Whether HAART allows complete recovery of humoral immune function in HIV-infected individuals is still controversial. Our objective was to study the effect of HAART on both B cell repopulation and hypergammaglobulinemia in 72 naïve patients, including 35 HCV-coinfected individuals, during 156 weeks on HAART. The possible role of HCV coinfection on the recovery of the humoral immune system was also investigated. At baseline, HCV-coinfected patients had greater circulant IgG levels than HIV-only-infected patients, while B cell count and CD21(low) B cell subpopulation were similar in both groups. During HAART, HIV-only-infected patients reached normal B cell counts and circulant IgG levels, while HCV-coinfected individuals did not. CD21(low) B cell subpopulation significantly decreased in both groups of patients at week 48 after the initiation of HAART compared to baseline. Thus, B cells remained continuously stimulated in HCV-coinfected patients and this stimulation seemed to be through a CD21-independent pathway.