This exploratory study assessed medication adherence and its correlates in HIV-positive members of HIV mixed status couples. Forty couples were interviewed; the HIV-positive participants consisted of 19 gay men, 14 heterosexual men and seven heterosexual women. Mean self-reported adherence (over the past three days) for the whole sample was 95%; the mean adherence rate for gay men (99%) was significantly higher (p < 0.05) than that of heterosexual men (94%) and heterosexual women (87%) based on a ranked transformation of the adherence score. In analyses involving measures rated by the HIV-positive partner, higher adherence was associated with more years of education, greater perceived treatment efficacy, stronger belief that combination therapy is a significant advancement in treatment, and greater knowledge of HIV treatments and consequences of poor adherence. Higher adherence was associated with the HIV-negative partner attributing less risk to unprotected anal/vaginal sex within the couple, while lower adherence was associated with a greater likelihood that the couple engaged in unprotected anal/vaginal sex in the last two months. A larger sample is needed to substantiate these findings.