Major opium trafficking routes traverse rural Iran, but patterns of drug use and HIV infection in these areas are unknown. In 2004, Iran's Ministry of Health integrated substance use treatment and HIV prevention into the rural primary health care system. Active opium or heroin users (N = 478) were enrolled in a rural clinic. Participants received counseling for abstinence from substances, or daily needle exchange and condoms. On enrollment, 108 (23%) reported injecting; of these, 79 (73%) reported sharing needles. Of 65 participants tested for HIV, 46 (72%) tested positive. Participants who received daily needle exchange/condoms stayed in the program longer than those who did not (AOR 2.08, 95% CI 1.1-3.88). This project demonstrates that HIV risks exist in rural Iran and suggests the innovative use of Iran's rural health care system to extend prevention and treatment services to these populations.