Improved treatment-adherence support programs are needed to help human immunodeficiency virus (HIV)-infected persons comply with complex highly active antiretroviral treatment (HAART) regimens. In an experimental directly administered antiretroviral therapy (DAART) program, treatment-naive and treatment-experienced persons who experienced failure of no more than 1 prior regimen were recruited from 3 public HIV/AIDS clinics in Los Angeles County. For 6 months, trained community workers observed ingestion of 1 of 2 daily HAART doses, 5 days per week, and questioned the patient about the second dose, which enabled intense adherence monitoring and real-time intervention. From November 2001 through November 2003, there were 67 DAART patients enrolled (69% Latino, 21% African American, and 9% white; 63% with annual income of <10,000 dollars). Preliminary findings show that a DAART program based in 3 public HIV/AIDS clinics was feasible in a low-income urban population. Effective communication between the DAART staff, the medical providers, and the pharmacy is essential for the successful implementation of this program.