In a confidential medication adherence questionnaire completed by 255 participants in the HIV Outpatient Study (HOPS) between March and November 1999, 33% reported skipping antiretroviral doses within the previous 3 days. The respondents, with a median age of 41, were predominantly male (86%), white (62%), and highly educated (33% had some post-high school training but no college degree and 39% had a college degree; only 11% had less than a high school diploma). Twenty-one percent had a history of injection drug use, 12% were unemployed, and 18% had Medicaid insurance. Questions about difficulty taking antiretroviral medications or drug holidays identified an additional 16% of patients experiencing adherence problems and explained significantly more of the failure to achieve undetectable viral loads than simply querying about skipped doses.