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The present study sought to investigate the impact of life stress on treatment adherence and viral load of HIV-positive individuals. Three different aspects of life stress were examined in this investigation (perceived stress, acute life events unrelated to the HIV illness, and HIVrelated acute life events). Furthermore, we examined whether these relationships were moderated by depressive severity, self-esteem, and neuroticism. Participants (n = 24) were treatment- seeking HIV-positive individuals who completed a series of questionnaires for this investigation. The majority of the participants in this sample were middle-aged, Caucasian males who identified themselves as either homosexual or bisexual, had contracted HIV via sexual contact, and met criteria for AIDS (mean CD4 count = 324). This sample was highly self-selected and varied from the county HIV-positive population in terms of gender, ethnicity, and HIV risk factor. Information on their adherence and viral load was collected from their medical records 6 to 9 months after completion of the psychological measurements. Results indicated that perceived stress, but not acute events, prospectively predicted adherence. Moreover, marginal trends suggested that depressive symptoms and neuroticism moderated the effect of perceived stress on adherence. Neither perceived stress nor acute life events were associated with viral load.