To ascertain whether immune complex dissociation (ICD) improves the value of p24 antigen as a prognostic marker for progression of HIV infection, 53 patients were followed over a 3-year period, including at least one visit per year. All had CD4+ counts at entry > 400/mm3; progressors (n = 18) were defined as having CD4+ counts < 200/mm3 and nonprogressors (n = 35) as having CD4+ counts still > 400/mm3 at the end of follow-up. Serum specimens were collected at each annual visit and assayed for p24 antigen with and without ICD treatment. At entry, the percentage of progressors positive for ICD p24 antigen was significantly higher than the percentage of positive nonprogressors (39% versus 3%, p < 0.01). The sensitivity of p24 antigen over all visits in terms of predicting the progression increased from 61% before ICD to 83% after. The specificity of p24 antigen in terms of predicting progression decreased from 97% before ICD to 89% after. The relative risk of progression in individuals positive for p24 antigen was 6.7 before ICD and increased after ICD to 12.7. When evaluating the respective prognostic value of the p24 antigen and of the ICD p24 antigen, only ICD p24 was significant (RR 10.2, 95% CI 2.2-46.9). ICD p24 antigen appears to be a marker of progression that may be detected earlier than p24 antigen without ICD.