The authors investigated the effect of IVIg on T-cell proliferation induced by the superantigen, staphylococcal enterotoxin B (SEB). The addition of IVIg to normal PBMC stimulated with SEB resulted in a threefold increase in the proportion of CD3+ blast cells expressing V beta 3 and V beta 17, two subsets of T cells that selectively expand in the presence of SEB. There was no increase in the proportion of T-cell blasts expressing V beta 2, V beta 8 and V beta 13.6 antigens that do not respond to SEB in the absence of IVIg. As described previously, IVIg inhibited T-cell proliferation independently of V beta specificity. The effects of IVIg were mediated by variable regions of immunoglobulins since they were reproduced with F(ab')2 fragments of IVIg but not with purified Fc fragments of IgG. The observation that SEB-activated T cells are rescued from inhibition of proliferation by IVIg indicates that Mg modulates the effects of superantigen on T cells. These results may be of relevance for understanding the mechanisms underlying the effects of IVIg in patients with diseases in which T-cell superantigens are of pathophysiological significance.