The plasma concentration and distribution of apolipoprotein A-IV were investigated in normotriglyceridaemic patients with end-stage renal disease and compared with those in a sex- and age-matched control group with normal renal function. A three-fold elevated plasma mean concentration of apolipoprotein A-IV was found in patients with end-stage renal disease treated by haemo- or peritoneal dialysis (58.5 +/- 18.9 mg dl-1 or 50.5 +/- 12.2 mg dl-1, respectively) compared with the controls (18.3 +/- 6.4 mg dl-1). The plasma distribution of apolipoprotein A-IV was studied in patients treated by haemodialysis and in controls by gel permeation chromatography. In the haemodialysis group, 40.3% of the apolipoprotein A-IV was found to be associated with the fraction of high density lipoproteins, whereas the rest (59.7%) was not associated with lipoproteins. This distribution was significantly different from that in the control group (24.8% vs. 75.2%, 0.01 less than P less than 0.05). The elevated plasma concentrations of apolipoprotein A-IV in the patients are not related to triglyceride levels and therefore are unlikely to result from an impaired catabolism of triglyceride-rich lipoproteins. The accumulation of apolipoprotein A-IV in high density lipoproteins from patients with end-stage renal disease might reflect the impaired reversed cholesterol transport mechanisms which are believed to be a major cause of the high prevalence of atherosclerotic diseases in these patients.