In the present study we found that antiphospholipid activity in sera from patients with anticardiolipin antibodies was inhibited in vitro by therapeutic polyspecific normal immunoglobulins (IVIg). In fact, F(ab')2 fragments from IVIg (IVIg-F(ab')2) inhibited the binding of anticardiolipin antibodies to the corresponding antigen in a dose-dependent fashion, thus suggesting that the interaction between IVIg-F(ab')2 and anticardiolipin antibodies occurred within or near the antigen combining site. The maximal inhibition ranged from 35.25 +/- 5.56 to 64 +/- 5.48%. In addition, patients' IgG containing antiphospholipid activity specifically bound insolubilized IVIg-F(ab')2, as assessed by enzyme-linked immunosorbent assay (ELISA). These results indicate that IVIg obtained from a large pool of normal donors contain anti-idiotypic antibodies directed against idiotypes located on antiphospholipid antibodies. Moreover, our observations suggest that the reported favourable effect of high dose infusion of IVIg in patients with recurrent abortions due to antiphospholipid antibodies may depend, at least in part on inhibition of the binding of such autoantibodies to the corresponding antigens (s) and/or inactivation of idiotype bearing B cell clones.