Dietary, serum, and tissue levels of copper and zinc were determined at baseline in a cohort of homosexual men to investigate the relationship of these factors to human immunodeficiency virus type 1 (HIV-1) seropositivity and subsequent progression to AIDS. Using a nested case control design, 54 asymptomatic HIV-1 seropositives who later progressed to AIDS were compared with 54 HIV-1 seropositives who did not progress and 54 seronegatives (mean follow-up time 2.5 years). Serum levels of copper and zinc were estimated from frozen serum samples, tissue levels from stored toenail samples, and dietary intakes from a semiquantitative food frequency questionnaire administered at baseline. Neither dietary copper and zinc nor their levels in toenails were associated with HIV-1 seropositivity or progression to AIDS. However, serum copper levels were higher (p = 0.002) in HIV-1-seropositive progressors (mean = 115.6 micrograms/dl; SD = 17.1) than the seropositive nonprogressors (mean = 109.0 micrograms/dl; SD = 15.8) and the seronegatives (mean = 101.9 micrograms/dl; SD = 16.7). Conversely, serum zinc levels were lower (p = 0.016) in the seropositive progressors (mean = 85.2 micrograms/dl; SD = 11.5) than the seropositive nonprogressors (mean = 90.7 micrograms/dl; SD = 12.0) and the seronegatives (mean = 92.0 micrograms/dl; SD = 14.7). Furthermore, in a logistic regression, higher serum copper (odds ratio per 20-micrograms/dl increase = 2.23; 95% confidence interval = 1.02-4.87) and lower serum zinc (odds ratio per 20-micrograms/dl increase = 0.30; 95% confidence interval = 0.14-0.66) predicted progression to AIDS independently of baseline CD4+ lymphocyte level, age, and calorie-adjusted dietary intakes of both nutrients.(ABSTRACT TRUNCATED AT 250 WORDS)