The Western blot is the most widely used confirmatory test for determining human immunodeficiency virus (HIV) seropositivity. Specific bands in the Western blot indicate antibody responses to various portions of HIV or its precursors, and each is assigned a score from 0 to 3+. While the precise role of humoral antibody responses has not been fully established, specific antibody responses might influence the course of HIV infection. This study investigated the association between antibody reactivity to nine principal Western blot bands and initial CD4+ counts among 877 Navy and Marine Corps personnel during 1988 to 1991. Multiple regression was used to evaluate the strength and significance of the associations and to adjust for age and estimated duration of infection. Strong antibody responses to the p24 core (P < 0.05), p53 reverse transcriptase (P < 0.005), and p55 core precursor (P < 0.0001) antigens were associated with higher initial CD4+ counts, with 33 to 48 additional cells/mm3 associated with each unit increase in the Western blot score, according to a multiple regression analysis which controlled for age and duration of infection (maximum 24 months). By contrast, antibodies to the gp41 transmembrane antigen (P < 0.0001) were associated with lower initial CD4+ counts. Each unit increase in the gp41 band was associated with 76 fewer CD4+ cells/mm3. A negative association was also observed for the gp160 envelope precursor antigen, with each unit increase in reactivity associated with 51 fewer CD4+ cells, although this association was not statistically significant (P = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)