Our objective was to map serial patterns of Western blot reactivity over time of a cohort of initially ELISA-negative, Western blot-indeterminate individuals from a high-risk group and to determine if these individuals were at increased risk of harboring occult HIV-1 infection. A 2-year prospective study used serial ELISA, two types of Western blot, immunologic profiles, HIV-1 culture, and analysis by polymerase chain reaction. Subjects were 20 ELISA-negative, Western blot indeterminate homosexual volunteers and 20 matched seronegative controls. Results showed that 19 of 20 study subjects completed a mean of 17.0 months of clinical and laboratory follow-up. Reactivities with p24 and/or with p55 were the two most commonly observed Western blot patterns, occurring in 70% of individuals. Specific Western blot reactivity was dependent upon the particular immunoblot preparation being used and varied considerably on a longitudinal basis. No individual pattern appeared predictive of an increased likelihood of subsequent seroconversion to HIV-1 relative to controls. By all other criteria including polymerase chain reaction analysis, samples from 17 of 19 individuals remained negative for HIV-1 at each time point. Two individuals evolved from an indeterminate to a positive Western blot and, simultaneously, from a negative to a positive polymerase chain reaction analysis, during follow-up. Our conclusions were as follows. ELISA-negative, Western blot-indeterminate individuals from a high-risk group show marked variability in immunoblot findings over time, and these patterns do not appear predictive of an increased likelihood of infection.(ABSTRACT TRUNCATED AT 250 WORDS)