We have assessed the diagnostic value of site-directed bronchoalveolar lavage (BAL) and combined transbronchial biopsy (TBB) in 29 HIV-infected patients with localized pneumonia, in whom a previous BAL was nondiagnostic and in whom improvement did not occur with empiric antibiotic therapy. All patients but three had a CD4 cell count < 100/microliters. A definite diagnosis could be reached in 26 of 29 (90%) individuals, including 24 pathogens. Neither the radiologic pattern nor the type of Pneumocystis carinii (PC) prophylaxis could predict the positivity of either one of these two diagnostic procedures. Site-directed BAL alone allowed a diagnosis in infection in eight (28%) cases. TBB alone led to diagnosis in eight (28%) cases, including three PC and two toxoplasma gondii, undiagnosed by the site-directed BAL. Both techniques were positive and in agreement in 10 (34%) cases. The majority of the diagnosis led to a specific treatment. Therefore, the patients' survival was positively altered by the procedure. In conclusion, the performance of site-directed BAL and combined TBB markedly optimizes the diagnostic yield of each of these procedures performed separately in HIV-infected patients with localized pneumonia.