The occurrence of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus type 1 (HIV-1)-infected individuals with high CD4+ counts indicates poor immunologic function. Thrush and persistent fever, easily recognized clinically, are potential measures of immunocompetence. This analysis establishes the complex interactions of CD4+ count, thrush, and persistent fever to predict the occurrence of PCP. Analyses used 20,632 person visits from 2,568 HIV-1-seropositive homosexual or bisexual men participating in the Multicenter AIDS Cohort Study (MACS). Comprehensive examinations were conducted semiannually, while occurrences of PCP were assessed continuously. The occurrence of thrush and fever increase in frequency as CD4+ levels decrease. The relative hazard of PCP in the presence of thrush compared with the absence of thrush rises (p < 0.05) from 1 for the lowest CD4+ category to approximately 5 in the highest categories. The relative hazard of PCP in the presence of fever compared with the absence of fever is above one (p < 0.05) in all CD4+ categories. No cases of PCP occurred in individuals on PCP prophylaxis with CD4+ counts > 200/mm3. These results suggest that HIV-1-related symptoms provide a measure of failing immune function that is not reflected by enumeration of CD4+ lymphocytes alone and support the United States Public Health Service recommendation that symptomatic individuals with CD4+ counts > 200/mm3 should be considered for PCP prophylaxis.