From a retrospective analysis of 85 patients with thrombocytopenia and HIV infection, in whom platelet production and destruction were studied by isotopic methods, the following conclusions are drawn. In most recently infected patients thrombocytopenia is due to accelerated platelet destruction; in these patients the platelet sequestration is predominantly splenic, and splenectomy is usually effective. The same pattern is seen in approximately one third of patients with more advanced disease (ie, those with AIDS-related complex or frank AIDS). In most patients with AIDS-related complex or AIDS, the thrombocytopenia is due chiefly to a platelet production defect; splenectomy is less likely to help and is thus generally inadvisable. When the patients who were receiving zidovudine were examined separately, they were found to have a lesser rate of platelet destruction but also to have a more prominent defect in platelet production defect. This suggests that the drug may help blunt platelet destruction but may do so at a price in marrow response to the thrombocytolysis.