108 seropositive homosexual men were examined for associations between HLA phenotype and progression of human immunodeficiency virus type 1 (HIV-1) infection. Among men of predominantly European ethnic origin, 49 with very rapid 2-year declines in CD4+ lymphocyte counts showed significant differences in antigen frequencies from 59 men matched for ethnic background, study centre, and initial CD4+ cell count but with little or no decline in CD4+ cells. Relations of varying strength (odds ratios 6.1-10.3) were seen with several HLA antigens often linked in the A1-Cw7-B8-DR3 haplotype. The strongest relation was with the A1, Cw7, B8 combination (odds ratio 10.3). Associations between these antigen combinations and development of AIDS were weaker. The frequency of HLA A24 was also significantly higher in rapid than in slow decliners (odds ratio 4.3). These findings strengthen the suggested link between the product of a gene in the A1-Cw7-B8-DR3 haplotype and HIV-1-related disease.