Sequential specimens obtained from 87 multicenter AIDS cohort study participants were tested by three p24 antigen tests. They included a polyclonal enzyme immunoassay (EIA), a monoclonal EIA, and a monoclonal EIA after immune complex dissociation (ICD) of specimens. Subjects were grouped into two categories defined by real-time testing with the polyclonal EIA: 39 had become positive for p24 antigen (antigen converters) during follow-up, and 48 had progressed to AIDS without detectable antigenemia. Twenty-four (61%) antigen converters were positive by ICD-monoclonal EIA about 1 year earlier than by monoclonal EIA. In contrast, only 12 (25%) patients who progressed to AIDS without detectable antigenemia became positive by ICD-p24 EIA before developing AIDS. Thus, the main benefit of ICD treatment may be to detect p24 antigenemia approximately 1 year before the regular assay rather than to identify additional antigenemic people. Quantitative plasma RNA levels were also determined in longitudinal samples from 20 antigen converters and 7 men who developed AIDS without antigenemia. Although mean human immunodeficiency virus type 1 RNA levels were higher in antigen-positive than in antigen-negative samples (P = 0.002), more than half (11 of 20) of the antigen converters had no measurable change in human immunodeficiency virus type 1 RNA associated with change to antigen positivity.