B cell dysregulation is a hallmark of human immunodeficiency virus infection. Since B lymphocytes comprise two distinct subpopulations, CD5+ and CD5- cells, we addressed their individual phenotypic and functional behavior. Seropositive patients with both limited and advanced disease progression had an increased percentage of peripheral blood CD5+ B cells, compared to seronegative controls (20.1 +/- 2.1 and 22.7 +/- 5.7, respectively, vs 17.0 +/- 3.4 in controls); however, due to the lymphopenia and reduced number of circulating B cells in infected individuals, the absolute number of CD19+CD5+ lymphocytes was actually reduced. Although HIV-specific antibodies were synthesized spontaneously in vitro only by CD5- B cells, a 10-fold lower degree of spontaneous, non-HIV-specific activation was also displayed by unstimulated CD5+ B cells. These findings indicate that B cell dysregulation during HIV infection involves both the CD5- and the CD5+ B cell compartments; moreover, in view of the putative role of CD5+ B cells in autoimmune phenomena and IL-10 production, these data reinforce the possibility that B cell dysfunction might be causally involved in AIDS pathogenesis.