In order to examine the role of endogenous opioid peptides on glucose metabolism in uraemic patients, plasma concentrations of beta-endorphin, glucose, insulin and C-peptide were determined before and during an oral glucose tolerance test (OGTT) in nine non-dialysed patients with chronic renal failure (CRF). The results are compared with those obtained in a group of age-matched normal subjects. In CRF patients, plasma beta-endorphin fasting values (16.0 +/- 1.9 pmol/l) were significantly higher than those of the controls (6.6 +/- 0.6 pmol/l) and significantly correlated with the degree of renal function impairment. After glucose load, plasma beta-endorphin in CRF patients tended to decline, whereas in normal subjects increased. The fasting and the mean OGTT plasma beta-endorphin values negatively correlated with insulin initial response to glucose, insulin and C-peptide mean OGTT values, but not with glucose OGTT mean values. Data indicate that chronic uraemia induces a significant increase in circulating plasma beta-endorphin levels, with a loss of opioid system responsiveness to glucose. The possibility that this hyper-endorphinism may have a biological importance at least as a contributory factor of impaired glucose tolerance in uraemia may be suggested.