The frequency of thrombocytopenia in patients with chronic renal failure (CRF) is controversial. This study was undertaken to investigate the platelet count in 55 patients with end-stage renal disease on maintenance hemodialysis and in 19 patients with CRF before hemodialysis had begun. In both groups platelet counts were similar and significantly reduced, 175,000 +/- 6,500 and 181,000 +/- 10,800 compared to 253,000 +/- 3,700/mm3 in the control (p less than 0.0001). 31% of hemodialysis patients had thrombocytopenia (platelet count less than 150,000/mm3). The megakaryocyte number in their bone marrow aspirate was not reduced. Primary renal disease, androgen treatment or parathyroidectomy did not affect the platelet count. Thrombopoietic activity using 75Se-selenomethionine incorporation into platelets measured in 7 thrombocytopenic patients was found to be reduced, 6.77 +/- 0.29 vs. 9.06 +/- 0.27 (X 10(-2)%: p less than 0.001). This study shows that the platelet count is reduced and mild thrombocytopenia is frequent in patients with CRF. A possible cause for the platelet count reduction is insufficient thrombopoietic activity.