Recombinant human erythropoietin is a successful treatment for the anaemia of renal failure. Its use has however been associated with thromboembolic complications. Changes in platelet number and behaviour in vitro were studied in: (1) 23 haemodialysis patients, and 10 continuous ambulatory peritoneal dialysis patients (CAPD) treated with erythropoietin (EPO); (2) 14 untreated dialysis patients (7 haemodialysis, 7 CAPD), with intrinsically high haemoglobins; and (3) 23 age-matched non-uraemic normal controls.All patients treated with erythropoietin had a significant rise in haemoglobin (23 haemodialysis patients: pre-EPO median (range), 6.9 (5.1–8.1)g/dl; post-EPO, 10.9 (9.0‐–12.8)g/dl; 10 CAPD patients: pre-EPO, 7.8 (6.7–8.8)g/dl); post-EPO, 12.5 (9.9–14.3)g/dl; p<0.01). Platelet number was significantly reduced in CAPD patients (pre-EPO: 327 (210-745)&109/1; post-EPO: 240(198–359)&109/l; p<0.01) but not in haemodialysis patients.Spontaneous and collagen-induced whole blood platelet aggregation were significantly increased following erythropoietin treatment, both in haemodialysis (spontaneous platelet aggregation: pre-EPO, 39(12–78)%; post-EPO, 64(27–93)%, p<0.01, collagen-induced platelet aggregation: pre-EPO, 61(3–95)%; post-EPO, 74(21–93)% p<0.05), and CAPD patients (spontaneous platelet aggregation: pre-EPO, 38(18–81)%; post-EPO, 71 (41–95)%, p<0.01, collagen-induced platelet aggregation; pre-EPO, 73(28–95)%; post-EPO, 90(44–95)%, p<0.05). There was no significant change in aggregation to 1μM ADP.Spontaneous and collagen-induced platelet aggregation were significantly higher in erythropoietin treated patients and untreated CAPD controls with high haemoglobins compared to age and haemoglobin-matched non-uraemic normal individuals (23 normals: spontaneous platelet aggregation, 37(10–75)%; collagen-induced platelet aggregation, 43(6–94)%, p<0.001).Enhanced platelet aggregability is associated with vascular disorders. The increased red cell mass due to erythropoietin therapy may have physical and chemical effects on platelet function predisposing to thrombosis in this susceptible group of patients.