Seven to 12% of HIV-infected patients have thrombocytopaenia. The pathophysiology of the thrombocytopaenia is not clear. It has been variously suggested that it may be caused by an increased peripheral platelet destruction, a defect in platelet production, or by a combination of these. The aim of the study was to elucidate the pathogenesis of HIV-associated thrombocytopaenia. We determined the mean platelet life span (MPLS) and calculated the turnover of autologous indium-111-labelled platelets in 17 HIV-positive patients, seven with thrombocytopaenia. The sites of sequestration of labelled platelets were quantified. The thrombocytopaenic patients had a very short MPLS (3.0+/-3.8 h) and a marked increase in platelet production (18.2+/-12.6x10(9)/l/h). The majority of these patients (5 of 7) had excessive sequestration of platelets in the spleen. Five of the patients with a normal blood platelet count had a shortened MPLS (109+/-23 h) and increased platelet turnover (3.8+/-1.2x10(9)/l/h), i.e. the increased peripheral platelet destruction was compensated for by increased platelet production. The other five patients with a normal platelet count had normal MPLS (195+/-11 h) and slightly increased platelet production (2.5+/-0.6x10(9)/l/h). We conclude that patients with HIV-associated thrombocytopaenia have increased peripheral platelet destruction. Platelet production is elevated but is insufficient to maintain a normal peripheral platelet count. In these patients platelets are predominantly sequestrated in the spleen. Patients with HIV infection and a normal blood platelet count may also have increased platelet production. This may be an early subclinical phase in the development of full-blown HIV-associated thrombocytopaenia.