The effects of highly active antiretroviral therapy (HAART) on immunoglobulin isotypes and immunoglobulin G (IgG) subclasses were studied in 12 patients in early stages of HIV-1 infection. Blood samples were obtained at enrollment and 2, 4, 8, 12, 24, 48, and 120 weeks after initiation of HAART. Immunoglobulin concentrations were determined by nephelometry, and anti-p24-specific IgG and IgG1 levels were determined by an enzyme immunoassay. Overall time changes were analyzed in analysis of variance models. IgG and IgG1 levels showed a marked overall decline, whereas other immunoglobulin isotypes and IgG subclasses did not change significantly. Anti-p24-specific IgG1 levels decreased considerably and significantly more in virus isolation-negative patients than in virus isolation-positive patients, as defined according to the ability to isolate HIV-1 from their CD4+ T cells after initiation of therapy. Anti-p24 IgG levels showed a similar but overall weaker decline in the two groups. However, the anti-p24 IgG1 level followed the biphasic decline in plasma viremia more closely than the anti-p24 IgG level, with an initial sharp decline that leveled off with time. These findings suggest that the main reduction in immunoglobulin levels is caused by reduced HIV-1-specific antigen stimulation rather than a general reduction in immune activation. Using anti-p24 IgG1 as a parameter of response to the effect of HAART merits further investigation.