We retrospectively analyzed data from 75 hospitalized patients with a first episode of Pneumocystis carinii pneumonia to compare the ability of four parameters, including admission serum albumin, serum lactate dehydrogenase (LDH), alveolar-arterial oxygen gradient, and the APACHE II score, to predict mortality and response to initial antipneumocystis therapy. The eight patients who died due to pneumocystosis and the 12 who failed initial antipneumocystis therapy had significantly higher admission mean APACHE II scores and serum LDH levels and lower mean serum albumin levels than did the 65 who survived and the 61 who responded to initial therapy (p less than 0.05 for each). Differences in mean alveolar-arterial oxygen gradients were not statistically significant with respect to survival or response to initial therapy. In a stepwise discriminant analysis of parameters associated with mortality, APACHE II score and LDH level were statistically significant (p less than 0.0001 for each). In a stepwise discriminant analysis of parameters associated with response to initial therapy, APACHE II score and LDH level were again statistically significant (p less than 0.0001, respectively). The addition of the alveolar-arterial oxygen gradient and serum albumin level did not further increase the predictive ability of the discriminant analyses. When analyzed alone, neither the alveolar-arterial oxygen gradient nor the serum albumin were statistically significant in each discriminant analysis. The APACHE II score combined with the serum LDH may be more useful than other parameters, singly or combined, to more closely match patients with regard to severity of illness due to first episode Pneumocystis carinii pneumonia when comparing experimental new therapies with standard agents.