When a pleural effusion has been determined to be exudative, additional evaluation is needed to determine its cause, and amylase, glucose, pH and cell counts should be measured.

- Red blood cell counts are elevated in cases of bloody effusions (for example after heart surgery or hemothorax from incomplete evacuation of blood).

- Amylase levels are elevated in cases of esophageal rupture, pancreatic pleural effusion, or cancer.

- Glucose is decreased with cancer, bacterial infections, or rheumatoid pleuritis.

- pH is low in empyema (<7.2) and may be low in cancer.

- If cancer is suspected, the pleural fluid is sent for cytology. If cytology is negative, and cancer is still suspected, either a thoracoscopy, or needle biopsy of the pleura may be performed.

- Gram staining and culture should also be done.

- If tuberculosis is possible, examination for "Mycobacterium tuberculosis" (either a Ziehl–Neelsen or Kinyoun stain, and mycobacterial cultures) should be done. A polymerase chain reaction for tuberculous DNA may be done, or adenosine deaminase or interferon gamma levels may also be checked.

The most common causes of exudative pleural effusions are bacterial pneumonia, cancer (with lung cancer, breast cancer, and lymphoma causing approximately 75% of all malignant pleural effusions), viral infection, and pulmonary embolism.

Another common cause is after heart surgery, when incompletely drained blood can lead to an inflammatory response that causes exudative pleural fluid.

Conditions associated with exudative pleural effusions:

- Parapneumonic effusion due to pneumonia

- Malignancy (either lung cancer or metastases to the pleura from elsewhere)

- Infection (empyema due to bacterial pneumonia)

- Trauma

- Pulmonary infarction

- Pulmonary embolism

- Autoimmune disorders

- Pancreatitis

- Ruptured esophagus (Boerhaave's syndrome)

- Rheumatoid pleurisy

- Drug-induced lupus

The most common causes of transudative pleural effusions in the United States are heart failure and cirrhosis. Nephrotic syndrome, leading to the loss of large amounts of albumin in urine and resultant low albumin levels in the blood and reduced colloid osmotic pressure, is another less common cause of pleural effusion. Pulmonary emboli were once thought to cause transudative effusions, but have been recently shown to be exudative.

The mechanism for the exudative pleural effusion in pulmonary thromboembolism is probably related to increased permeability of the capillaries in the lung, which results from the release of cytokines or inflammatory mediators (e.g. vascular endothelial growth factor) from the platelet-rich blood clots. The excessive interstitial lung fluid traverses the visceral pleura and accumulates in the pleural space.

Conditions associated with transudative pleural effusions include:

- Congestive heart failure

- Liver cirrhosis

- Severe hypoalbuminemia

- Nephrotic syndrome

- Acute atelectasis

- Myxedema

- Peritoneal dialysis

- Meigs' syndrome

- Obstructive uropathy

- End-stage kidney disease

Fibrothorax is diffuse fibrosis of the pleural space surrounding the lungs. It can have several causes including hemothorax, pleural effusion and tuberculosis. It may also be induced by exposure to certain substances, as with asbestos-induced diffuse pleural fibrosis. Idiopathic fibrothorax may also occur.

In fibrothorax, scar tissue is formed around the visceral pleura following inflammation due to pleural effusion or other pathology. The scar tissue lies in a sheet between the pleura, then fuses with the parietal pleura and the chest wall. Over time, generally the course of years, the fibrotic scar tissue slowly tightens, which results in the contraction of the entire hemithorax, and leaves the ribs immobilized. Within the chest, the lung is compressed and unable to expand, making it vulnerable to collapse. At the microscopic level, the scar tissue is composed of collagen fibers deposited in a basket weave pattern. The treatment for fibrothorax is decortication, the surgical removal of the fibrous layer of scar tissue. However, since many of the diseases and conditions resulting in fibrothorax are treatable, prevention remains the preferred method of managing fibrothorax.

Its cause is usually traumatic, from a blunt or penetrating injury to the thorax, resulting in a rupture of the serous membrane either lining the thorax or covering the lungs. This rupture allows blood to spill into the pleural space, equalizing the pressures between it and the lungs. Blood loss may be massive in people with these conditions, as each side of the thorax can hold 30 to 40% of a person's blood volume or 1.5 to 2 L per side in the average adult. Even minor injury to the chest wall can lead to significant hemothorax.

Less frequently, hemothorax occurs spontaneously. A major vascular cause of hemothorax is aortic dissection or rupture of thoracic aortic aneurysms. It may also follow surgical intervention in the thoracic area. Infrequently, patients with pneumothorax may develop spontaneous hemothorax. Spontaneous hemothorax or hemopneumothorax may be occur with endometriosis, if endometrial tissue implants on the pleural surface, then bleeds in response to cyclical hormonal changes in menstruating women.

A hemothorax is a type of pleural effusion in which blood accumulates in the pleural cavity. This excess fluid can interfere with normal breathing by limiting the expansion of the lungs. The term is from "" + "thorax".