The objective of this pilot study was to examine attitudes toward protease inhibitors (PIs) among HIV-infected individuals and to assess the relationship between PI attitudes and adherence to PIs. Respondents were recruited from four AIDS service organizations in New York City; the total sample consisted of 97 HIV-infected individuals who were taking a PI. The sample consisted largely of African Americans and Latinos from inner city areas, and most had a low level of education. Adherence was suboptimal, with more than 50% of respondents failing to take their PI medications exactly as prescribed within the previous month. Individuals who had recently used illegal drugs within the past 6 months were more likely to be nonadherent to PIs. Those who were not adherent to PI medications reported greater concern about the side effects of PIs and were more likely to believe that it was acceptable to skip doses of PIs.