During a 24-hour period, the serum levels of prolactin (PRL) were determined in 89 subjects, including 24 controls and 65 with chronic renal failure (CRF), divided into groups according to sex, age and serum creatinine. In mild CRF, both in males and females, PRL level proved to be higher than controls while its circadian rhythm of secretion disappeared. The MANOVA analysis (multivariate analysis of variance) showed that all 3 considered factors (sex, age, creatinine) have a systematic effect on PRL values, that of creatinine being the most prominent. With the progression of renal failure, the physiological PRL oscillations tended to diminish. In general, increasing creatinine levels progressively shifted the acrophase (that is the time-distance between a given hour and the maximum peak of the function) to the morning, with hemodialysis patients showing acrophases between 12 p.m. and 1 a.m. It is possible that in CRF the PRL feedback system could no longer function.