Previous studies compared the diagnostic value of pleural fluid cytology versus pleural biopsy. No direct comparison of the procedures including data from a combination of all diagnostic tests performed on each specimen appears to have been done. A total of 385 patients with concurrent pleural biopsy and fluid examination were identified from 1973 to 1986. Clinical records, histologic and cytologic preparations, and microbiologic and chemical data were reviewed. A total of 109 patients had a final diagnosis of malignancy. Cytology was diagnostic in 71% and "suggestive" in an additional 8%. There were no false-positives but, in two patients with pulmonary infarcts, the effusions were reported as "suspicious." Pleural biopsy was positive in 45%, including three cases with negative cytology. In 71 patients with tuberculosis, the pleural biopsy was diagnostic in 49%. A cytologic picture suggesting the diagnosis was present in 68%. Cultures of the biopsy yielded Mycobacterium tuberculosis in 23% of cases, while pleural fluid was positive in 30%. In six cases, the only confirmatory evidence of tuberculosis was pleural culture. In 205 patients, none of the above procedures provided specific diagnoses. A combination of biopsy and fluid examinations improves the diagnostic sensitivity. Pleural biopsy increases the rate of complications and did lead to fatal hemothorax in two patients. These results support the superiority of pleural fluid examination in the diagnosis of malignancy. In addition, they demonstrate the value of pleural fluid examination in the diagnosis of tuberculosis.