To evaluate the WHO (World Health Organization) algorithm for management of respiratory tract infection (RTI) in HIV-1-infected adults and determine risk factors associated with RTI, we enrolled a cohort of 380 HIV-1-seropositive adults prospectively followed for incident RTI at an outpatient clinic in Nairobi, Kenya. RTI was diagnosed when patients presented with history of worsening or persistent cough. Patients were treated with ampicillin, or antituberculosis therapy when clinically indicated, as first-line therapy and with trimethoprim/sulfamethoxazole as second-line therapy. Five hundred ninety-seven episodes of RTI were diagnosed: 177 of pneumonia and 420 of bronchitis. The WHO RTI algorithm was used for 401 (95%) episodes of bronchitis and 151 (85%) episodes of pneumonia (p <.001). Three percent of bronchitis cases versus 32% of pneumonia cases failed to respond to first-or second-line treatment (p <.0001). Being widowed (adjusted odds ratio [OR] = 2.1, 95% confidence interval [CI]: 1.0-4.4), less than 8 years of education (adjusted OR = 2.5, CI: 1.5 - 4.1), and CD4 count < 200 cells/microl (adjusted OR = 2.4, CI: 1.4-3.9) were risk factors for pneumonia. A high percentage of patients (32%) with pneumonia required a change in treatment from that recommended by the WHO guidelines. Randomized trials should be performed to determine more appropriate treatment strategies in HIV-1-infected individuals.