HIV-1 infection results in progressive failure of the immune system with decline in the number and/or function of B-cell clones originally recruited in specific humoral responses. Spectrotypic analysis, done by isoelectric focusing and reverse blotting (IEF-RB), is one technique for evaluating the activity and the number of specific B-cell clones and is adaptable to the direct measurement of antibodies to conformationally intact epitopes. The anti-HIV-1 (IIIB) rgp120 spectrotype was measured in 30 early-stage HIV-infected volunteers undergoing vaccine therapy with recombinant gp160 (rgp160). Twenty-five of the patients displayed a clear oligoclonal banding pattern; seven (28%) showed the same pattern in all samples, while 18 (72%) showed changes. Ten of the latter had an increase in band intensity over the course of immunization, and eight had an increase in both band intensity and number of bands. In contrast, serum samples from eight patients receiving placebo (alum) showed no changes over a comparable period. These findings suggest that vaccine therapy with rgp160 may be able to expand the anti-HIV-1 (LAI) gp120 B-cell clone pool in some HIV-infected patients as well as increase antibody synthesis by established B-cell clones recruited during natural infection. These data provide further evidence that postinfection vaccination may provide an alternative strategy in the-treatment of chronic viral diseases.