This study examines the role of uraemia and the effect of different dialysis treatments on red cell cation transport. We evaluated the main cation transport systems in erythrocytes of non-dialysed end-stage renal disease (ESRD) subjects, of patients undergoing haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD), as well as the changes induced by human recombinant erythropoietin (r-HuEPO) administration. In uraemic undialysed and dialysed patients, we observed an increase in K/Cl co-transport activity and in shrinkage-induced amiloride-sensitive (HMA-sensitive) Na efflux (Na/H exchange) and a decrease in Na/K pump and Na/K/Cl co-transport activity, while Na/Li exchange was increased only in dialysed patients. In uraemic erythrocytes, we showed for the first time an increased K/Cl co-transport activity, which was cell age independent. Generally, the different method of dialysis (CAPD or HD) did not modify the cation transport abnormalities observed. During the treatment with r-HuEPO, all the systems, with the exception of the Na/K pump and Na/K/Cl co-transport, increased their activities following the increase of circulating young red cells. The changes produced under r-HuEPO administration were transient and cation transports returned to the baseline values within 100 days of treatment, indicating a primary and prominent pathogenetic role of uraemia in modulating the red cell membrane cation transport activities.