IVIg are increasingly used for the treatment of autoimmune diseases. In the present study, we show that IVIg contain antibodies directed against CD5, a cell surface molecule of T cells which is also a marker of the autoantibody-producing CD20+ ('B-1') subset of B lymphocytes. Antibodies to the CD5 molecule were demonstrated in IVIg by the ability of therapeutic preparations of IVIg to inhibit the binding of labelled CD5 MoAb to the CD5-expressing human T cell line H9. Preincubation of H9 cells with IVIg or with F(ab')2 fragments prepared from IVIg resulted in dose-dependent inhibition of the binding of CD5 antibody. The presence in IVIg of antibodies to the CD5 molecule was further confirmed by the binding of IVIg to mouse L cells that expressed human CD5 molecules following a stable transfection with CD5 cDNA. Human CD5 antibodies in IVIg provide therapeutic immunoglobulin preparations with the potential of modulating T cell functions through CD5, and of regulating the expression of B cell subsets expressing CD5. This may have implications for the treatment of autoimmune diseases.