The losses of protein into dialysate have been considered a major limitation of maintenance peritoneal dialysis. We, therefore, undertook a comprehensive evaluation of protein losses in 30 patients undergoing maintenance intermittent peritoneal dialysis (IPD), 12 patients undergoing acute IPD, and 8 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The weekly loss of protein based upon the usual treatments per week was relatively similar with the three modes of dialysis. Protein losses during repeated dialyses were similar for a given patient, but there was repeated dialyses were similar for a given patient, but there was marked interpatient variation. During maintenance IPD, protein loss was 12.9 +/- (SD) 4.4 g per 10 hours of dialysis; albumin loss was 8.5 g, and IgG loss was 1.3 g. Approximately 50% of the protein loss was from the ascitic fluid accumulated during the interdialytic interval, and concentrations of most proteins in the ascitic fluid correlated with their serum levels. Serum protein concentrations were in the low, normal range and did not change during dialysis. The development of peritonitis markedly increased protein losses. During acute IPD, 23.3 +/- 16.5 g of protein were lost per 36 hours of dialysis, lower losses than those previously reported. With CAPD, 8.8 +/- 1.7 g of protein were removed per 24 hours; also immunoglobulin losses correlated with their serum concentrations. The results of these studies suggest that, in the absence of peritonitis, dialysate protein losses do not appear to limit the usefulness of peritoneal dialysis.