To understand better the interaction between surfactant protein A (SP-A), human immunodeficiency virus (HIV) and Pneumocystis carinii pneumonia (PCP), we measured SP-A from bronchoalveolar lavage (BAL) fluid in immunosuppressed patients (HIV-positive [HIV+] and HIV noninfected [HIV-]) who were examined for possible pneumonia. Forty-five HIV+ patients, 16 with PCP and no other pathogen (HIV+/Pc) and 29 with no evidence of pulmonary pathogen (HIV+ controls), were compared with 6 HIV- patients with PCP (HIV-/Pc) and 11 control patients with no underlying disease (controls). Despite a similar inflammatory response in the HIV-infected patients whether they had PCP or not, we found increased BAL SP-A concentrations in HIV+/Pc patients as compared with HIV+ control patients (HIV+/Pc: median, 10.3 micrograms/ml; range, 2.8 to 24.3 micrograms/ml; HIV+ control: median, 1.9; range, 0.06 to 3.83 micrograms/ml; p < 0.05). The amount of SP-A in the HIV+ control group was significantly lower than healthy, uninfected volunteers, suggesting that HIV itself may lower SP-A levels. Six HIV+/Pc patients underwent BAL after 21 days of therapy and showed complete resolution of the P. carinii organism. There was a significant drop in the amount of SP-A at follow-up lavage (initial mean, 14.1 micrograms/ml; follow-up mean, 7.4 micrograms/ml; p < 0.02). We also found a significant correlation between the amount of P. carinii and the amount of SP-A in the BAL fluid (Spearman rank, 0.74; p < 0.01). We conclude that SP-A content is increased in HIV+ patients with PCP. The relationship between SP-A concentration and the abundance of P. carinii present in the BAL fluid may be related to SP-A binding to P. carinii or to alterations in surfactant protein homeostasis.