To determine the relationship of combination antiretroviral therapy and bacterial pneumonia, we assessed incidence of and risk factors for bacterial pneumonia in 1,898 human immunodeficiency virus (HIV)-infected patients with CD4 cell counts < 200/mm(3) followed in the Johns Hopkins HIV clinic between 1993 and 1998. A total of 352 episodes of bacterial pneumonia occurred during 2,310 patient-years of follow-up. Incidence of bacterial pneumonia decreased from 22.7 episodes/100 person-years (py) in the first half of 1993 to 12.3 episodes/100 py in the first half of 1996, reaching a nadir of 9.1 episodes/100 py in the second half of 1997 (p < 0.05). The use of protease inhibitor-containing regimens was associated with a decreased risk of bacterial pneumonia (risk ratio [RR] 0.55, 95% CI 0.31 to 0.94). Lower CD4 cell counts (RR 2.22, 95% CI 1.54 to 3.18), injection drug use as HIV transmission category (RR2.0, 95% CI 1.43 to 2.76), and prior Pneumocystis carinii pneumonia (RR 3.88, 95% CI 1.65 to 9.16) were also significantly associated with bacterial pneumonia. Trimethoprim-sulfamethoxazole and macrolide use were not significantly associated with risk of bacterial pneumonia. There has been a dramatic decline in the incidence of bacterial pneumonia resulting from the use of combination antiretroviral therapy containing protease inhibitors.