Nonnucleoside reverse transcriptase inhibitors (NNRTIs), particularly nevirapine, have been associated with hepatotoxicity. We performed a retrospective study to determine the incidence of NNRTI hepatotoxicity in a group of HIV-infected patients from a New York City practice. These patients are predominantly homosexual white males. We also analyzed the effect of coinfection with hepatitis B (HBV) or hepatitis C (HCV) virus. In total, 272 patients received NNRTIS: 40 (15%) received delavirdine, 91 (33%) received efavirenz, and 141 (52%) received nevirapine. Of the patients with known hepatitis status, 18 of 190 (9%) were coinfected with HBV, and 24 of 205 were coinfected (12%) with HCV. The overall rate of grade 3 to 4 elevations in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) was 3 of 272 (1.1%) and did not differ significantly among the three NNRTIs. HBV or HCV was not associated with a significant increase in AST or ALT elevations. We conclude that NNRTIs are relatively free from hepatotoxicity in this population, despite the presence of coinfection with HBV or HCV.