An increase in serum lactate dehydrogenase (LDH) activity is commonly taken to support the presumptive diagnosis of Pneumocystis carinii pneumonia (PCP), although the LDH level may also be increased in other lung infections and in a variety of extrapulmonary disorders. To assess its diagnostic value in patients with fever, lung infiltrates, and a high prevalence of HIV infection, we compared LDH levels in 42 hospitalized patients with PCP, 71 with disseminated tuberculosis (TB), 40 with pulmonary TB, and 37 with bacterial pneumonia. Peak LDH level was higher (p < 0.05) in patients with PCP (547 +/- 157 U/L) and disseminated TB (569 +/- 338 U/L) than in patients with pulmonary TB (258 +/- 66 U/L) or bacterial pneumonia (331 +/- 139 U/L). However, substantial overlap between groups limited its diagnostic value for individual patients. Expressing LDH as its ratio to simultaneous serum aminotransferases (AST or ALT) did not enhance its discriminatory value. Most patients in each group had abnormalities in other serum enzymes (AST, ALT, alkaline phosphatase, gamma-glutamyltransferase), making an isolated elevation of LDH level uncommon (21% of PCP cases). Serum LDH has a high sensitivity for PCP (100% in this series) but must be interpreted with caution given its lack of specificity.