An exploratory study was conducted with 27 injecting drug users (IDUs) on psychosocial factors (stress, coping reactions, and attitudes toward HIV illness and treatment) which are relevant to treatment acceptance and adherence. A semi-structured interview was used to collect qualitative data in a sample of 13 seropositive and 14 seronegative subjects. The results indicated a range of HIV-specific stressors such as social stigma, uncertainty about the future, disclosure of seropositive status, and monitoring of HIV illness. Seeking of social support, relapse to substance abuse, and mental disengagement were the most common coping reactions reported by the sample; there was a lack of behavioral, problem-focused responses. The study also provided descriptive information on attitudes toward HIV treatment, including fatalism, optimism (hope and control), and ambivalence regarding treatment efficacy. Clinical implications and suggestions for future research are discussed.