The role of adipose tissue lipoprotein lipase (LPL) in the pathogenesis of hypertriglyceridemia in uremic patients receiving maintenance hemodialysis was evaluated. The fasting level of adipose tissue LPL activity was reduced below normal (3.4 +/- 2.5 microU/106 cells; n = 23; mean +/- SD) in hypertriglyceridemic dialysis patients (1.5 +/- 0.8; P less than 0.01; n = 15) and did not differ from normal in normotriglyceridemic dialysis patients (2.5 +/- 2.4; P = NS; n = 13). The enzyme activity increased as a function of relative body weight in normotriglyceridemic hemodialysis patients (r = 0.21; P less than 0.05) but not in the hypertriglyceridemic group (r = 0.21; P = NS). There was an abnormal response of LPL to feeding in the hypertriglyceridemic dialysis patients. The postprandial level of LPL was significantly lower in hypertriglyceridemic dialysis patients (2.2 +/- 1.0; n = 9) than in normotriglyceridemic dialysis patients (3.9 +/- 1.9; P less than 0.05; n = 10) or normal controls (4.8 +/- 1.8; P less than 0.01; n = 12). Whereas the postprandial change in LPL was inversely related to the fasting enzyme activity in normotriglyceridemic dialysis patients (r = 0.74; P less than 0.02; n = 10) and in normal controls (r = 0.58; P less than 0.05; n = 12), no such relationship existed in hypertriglyceridemic dialysis patients (r = 0.17; P = NS; n = 9). Furthermore, fasting plasma triglyceride levels in the entire group of dialysis patients were a function of the postprandial level of LPL activity (rs = 0.574; P less than 0.02; n = 19). Since the level of LPL 1) is below normal in both the fasted and fed state in the hypertriglyceridemic hemodialysis patients, 2) is normal in both the fasted and fed state in the normotriglyceridemic hemodialysis patients, and 3) in the fed state is inversely correlated with the fasting plasma triglyceride concentration in the entire group of hemodialysis patients, it is proposed that adipose tissue LPL plays a role in the etiology of hypertriglyceridemia in hemodialysis patients.