HIV infection is associated with polyclonal increase in serum immunoglobulins and with elevated titers of serum antibodies to a variety of self antigens, including anti-phospholipid antibodies. In the present study, we found a high prevalence of 46.8% of serum IgG anticardiolipin antibodies (ACA) in a group of 111 unselected HIV-seropositive individuals. The presence of ACA was correlated with that of IgG antibodies to endothelial cells (AECA) but not with that of anti-beta 2 glycoprotein I antibodies, that were only found in 7.4% of the patients. The presence of IgG ACA was not associated with detectable lupus anticoagulant activity, nor with a history of thrombosis. Serum titers of ACA were not correlated with absolute numbers of circulating CD4+ cells. We found no relationship between the presence and titers of ACA, hypergammaglobulinemia, and serum titers of natural IgG autoantibodies to a panel of self antigens. Our results suggest that increased titers of ACA in HIV infection result from a biased expansion of B cell clones producing natural autoantibodies.