Several retrospective and prospective studies confirmed the beneficial effect of dietary protein restriction (DPR) on the downhill course of renal function in chronic kidney disease. The long-term results of this therapeutic modality may be different than the short-term effects. In our nephrology outpatient department, a prospective randomized trial has been in progress since April, 1982. In 1984, we reported a general beneficial effect of our diet after two years of follow-up. Two hundred and forty-eight patients with initial creatinine clearances between 10 and 60 ml/min entered the trial. Patients were stratified for sex, age and degree of renal insufficiency. One hundred and twenty-nine patients were randomly assigned to a DPR-group (0.4 to 0.6 g/kg/day); 118 patients to a control group. Patients on DPR visited the dietitian every three months during the first 24 months of the study; thereafter, as with the controls, the dietitian visits were only for specific needs. Urea excretion decreased significantly in DPR patients as a sign of good compliance and stayed at that level, even without frequent visits to the dietitian. Biochemical parameters showed no signs of malnutrition. Amino acid profiles were related to the degree of renal failure. The diet appeared to have a selective effect on the progression rate of renal failure: only patients with primary glomerular disease responded to the diet. Furthermore, there were striking intersex differences. Males showed a more rapid decline towards end-stage renal failure, but responded in a positive way to the diet, whereas female patients did not benefit from the dietary manipulation at all.(ABSTRACT TRUNCATED AT 250 WORDS)