A retrospective investigation was undertaken in which the rate of decline of residual renal function (RRF), estimated from creatinine clearance, was compared in 55 continuous ambulatory peritoneal dialysis (CAPD) and 57 hemodialysis (HD) patients for whom a minimum of four (mean of 7.6) well-spaced historic measurements of residual clearance were available. Because of the intrinsic variability that attends such data, specialized nonlinear, growth curve statistical methods were employed. Residual function was found to decline exponentially after the onset of therapy in both cohorts. The rate of decline in the HD group was twice that of the CAPD group (5.8% +/- 0.4% per month for HD vs 2.9% +/- 0.3% per month for CAPD; difference significant at p less than 0.0001). This difference remained highly significant (p less than 0.01) when corrected for other potential risk factors such as age, gender, hypertensive status, and use of angiotensin converting enzyme inhibitors in patients with diabetic or other forms of glomerular nephropathy. Differences between cohorts were not significant for patients with other diagnoses (p greater than 0.1) although the size of some of these subsets was very small. The physiologic mechanism for the more rapid fall-off of RRF on HD remains speculative, but could be related to renal ischemia secondary to intratreatment hypovolemia and/or to nephrotoxic effects of the inflammatory mediators of extracorporeal circulation.