Thrombocytopenia due to drug-dependent antibodies most frequently occurs with quinine/quinidine and with heparin. Considerable evidence has accumulated about the mechanism of action of quinine/quinidine-induced antibodies but less is known about the effect of heparin. Although there is controversy, it is likely that the action of quinine/quinidine-induced antibodies follows a loose association between drug and platelet with antibodies acting independently of the Fc receptor. There is strong evidence that the complex of glycoprotein Ib and glycoprotein IX, absent in the Bernard-Soulier syndrome, provides the binding site for quinine/quinidine-dependent antibodies. It also appears that the two glycoproteins must be present in complex form for antibody binding to occur. There is some heterogeneity of quinine/quinidine-dependent antibodies since there are reports of a proportion of patient antibodies reacting with other membrane determinants or acting independently of the drug. Heparin-induced thrombocytopenia may be the consequence of a direct effect, or a more serious condition associated with thrombosis may occur when heparin-dependent antibodies are formed. The mode of action of these antibodies and the nature of their antigenic determinants remain unclear. Recognition of heparin-associated thrombocytopenia is important so that serious bleeding or thrombotic sequelae can be forestalled.