Eleven chronic renal failure patients and 11 matched controls, received growth hormone GHRH (1-mu-g/kg iv) or TRH (400-mu-g iv) on separate occasions, immediately before undergoing hemodialysis. GHRH-induced GH peak in uremics (22.7 +/- 5.2-mu-g/l) was not different from that obtained in control subjects (16.0 +/- 4.3-mu-g/l). However, the uremic patients did not show the habitual post-peak fall, remaining GH levels over 10-mu-g/l till the end of the test. Differences between the two groups were significant (p < 0.05). Uremic patients showed PRL values higher than in controls, however their TRH-induced PRL peak (20.6 +/- 6.6-mu-g/l) was not different from that of controls (26.5 +/- 3.0-mu-g/l). Again chronic renal failure patients showed PRL plasma values abnormally elevated till the end of the test. Differences between the two groups were significant (p < 0.05). Administration of placebo to a different group of seven uremic patients did not alter GH and PRL plasma levels. This sustained secretion of both GH and PRL in uremia could be attributed to reduced kidney clearance. However, when subjects were examined individually both the GHRH- and the TRH-induced hormonal peaks and the subsequent fall were not different in both groups. Unlike with controls, in uremic patients GHRH-stimulated GH and TRH-stimulated PRL/GH peaks were dispersed throughout the 120 min period. In controls GH and PRL peaks clustered around 15-30 min. The peak dispersion created a false impression of flattened curves or sustained hyper-secretion in uremia. In conclusion, though we cannot rule out an altered hormonal clearance as contributing mechanism, the abnormal GH or PRL secretion after either TRH or GHRH administration in uremia suggest a hypothalamo-pituitary alteration. In endocrine studies with large peak dispersion the method of representation of mean +/- SE could be extremely misleading.