Protein-energy malnutrition occurs in patients with chronic renal failure primarily due to loss of appetite. The ob gene protein, leptin, which is secreted by adipocytes, regulates body composition by lowering food intake. We have measured plasma leptin in undialysed and dialysed patients and in controls and the concentrations have been related to body composition, dietary intake, and biochemistry. Plasma leptin was measured by radioimmunoassay in 93 individuals in groups of undialysed, peritoneal dialysed, and haemodialysed patients and controls. Body composition was determined by DEXA. Protein-energy malnutrition was evident in non-dialysed and dialysed patients from low lean or fat tissues, plasma albumin and transferrin. A third of the dialysis patients were eating less than prescribed intakes. Leptin relative to total fat mass (ng/ml/kg) was significantly greater for patients than for controls, particularly the dialysed patients. Leptin was highly correlated with total, arm, leg, and all other fat measurements, e.g. r for leptin vsm % total fat was: undialysed 0.88, PD 0.81, HD 0.93, and controls 0.83 (P < 0.0001 for all). Dialysis patients with the highest leptin/fat mass ratio had low protein intakes and significantly lower lean tissue mass. Leptin/fat ratio correlated inversely with dietary intake e.g. with protein intake in g/day and marginally in g/kg of ideal weight/day. Leptin concentration was unrelated to plasma creatinine or residual renal function or to the protein 'nutritional indices', albumin and transferrin. Our data suggests that leptin is markedly increased in some patients with chronic renal failure. The association of increased leptin with low protein intake and loss of lean tissue is consistent with leptin contributing to malnutrition but a definitive role cannot be substantiated by this study.