The effect of dialyzer geometry, both flat plate (FP) and hollow fiber (HF), on platelet and granulocyte activation during dialysis with cuprophane membranes was studied in 12 patients. A subset of six patients was restudied after correction of their anemia with recombinant human erythropoietin (EPO). Granulocyte count and aggregation in vitro fell significantly (P less than 0.01) at 20 minutes of dialysis, followed by a gradual return towards pre-dialysis values at 240 minutes. Malondialdehyde (MDA), a product of free radical reactions generated by activated granulocytes, increased significantly during dialysis [predialysis MDA (median, range): 8.4 (5.8 to 11.6) nmol/ml, 240 minutes MDA: 9.7 (6.6 to 12.5) nmol/ml, P less than 0.01 Wilcoxon test). This increase, however, was not affected by dialyzer geometry or EPO therapy. Neither type of dialyzer was associated with significant platelet loss at the end of dialysis. Whole blood platelet aggregation in vitro (spontaneous and collagen-induced) decreased significantly, (P less than 0.01) during dialysis, the fall in spontaneous aggregation being significantly less following EPO therapy [spontaneous aggregation 240 minutes; pre-EPO: 34 (13 to 52)%; post-EPO 50: (16 to 76)%, P less than 0.01)]. The ratio of the platelet release proteins beta-thromboglobulin and platelet factor 4 increased significantly during dialysis, indicating platelet activation in vivo, although there was no effect of dialyzer geometry or EPO. Factor VIII von Willebrand Factor antigen, a putative marker of endothelial damage, was raised pre-dialysis, and increased further during dialysis, irrespective of dialyzer geometry or EPO. In conclusion, dialyzer geometry had no significant effect on granulocyte and platelet counts and activity during hemodialysis with cuprophane membranes.(ABSTRACT TRUNCATED AT 250 WORDS)