This is a competing continuation study of the medical consequences of HIV infection in drug abusers and homosexuals co-infected with HIV-1. Thrombocytopenia is a frequent occurrence in HIV-1 infected intravenous drug abusers (HIV-1-IIP). We have discovered a unique Ab in these patients which is capable of inducing platelet fragmentation and destruction in the absence of complement via the elaboration of H2O2 and other reactive oxygen species (ROS). This Ab is directed against a specific epitope of the platelet B3 integrin, GPIIIa49-66 and induces its effect through activation of platelet NADPH oxidase and platelet 12-lipoxygenase. The oxidative fragmentation of platelets requires Ca++ and Protein Kinase C activation, indicating a role for intracellular signaling. The physiologic requirement for this mechanism is yet to be determined. Cross-talk between platelet ROS and endothelial cells or other cells after platelet GPIIIa49-66 perturbation is a distinct possibility. Since patients with HIV-1-ITP respond to glucocorticoids as do classic autoimmune thrombocytopenic patients (whose platelets undergo Ab-opsonized phagocytosis by macrophages), we looked for the effect of glucocorticoids (Dexamethasone) on this new mechanism of Ab-induced platelet oxidation/fragmentation. Dexamethasone inhibits this effect as well. We therefore, propose to study the mechanisms of this disorder by: 1. Elucidating the signaling pathways involved in Ab-induced platelet oxidation/fragmentation. 2. Elucidating the mechanism of dexamethasone-induced inhibition of Ab-induced platelet oxidation/fragmentation. 3. Exploring the effect of anti-GPIIIa49-66 Ab on megakaryocyte production. 4. Exploring the possible pathophysiologic role of platelet cross-talk with other cells (endothelial, fibroblast, neutrophil, and macrophage) by a cell peptide reacting with platelet GPIIIa49-66 to release ROS capable of activating these cells.