To investigate whether short-term fasting influences hormone release from human pinealocytes, nocturnal melatonin (MT) secretion was studied before and at the end of a 2-day fast in seven normal subjects (group A). Serum MT was measured every second hour between 1800 and 0800 h, and the nocturnal MT secretion, as reflected by the MT incremental area (MT area appearing above the 1800 h level), was calculated and compared before and during the fast. MT excretion by the urine (between 2200 and 0700 h) was also determined before, during, and after the period of food deprivation. Body weight and blood glucose concentration fell by 2.5 +/- 0.2 kg (mean +/- SEM, P less than 0.001) and 1.7 +/- 0.2 mmol/l (P less than 0.001) respectively during the fast. Nocturnal MT secretion declined by 19 +/- 3% (P less than 0.002), in contrast to urinary MT excretion which remained unaffected. In order to prevent blood glucose from falling significantly during the period of food deprivation, six additional normal subjects (group B) were given eight small oral doses of glucose (each dose 0.5 g/kg) at regular intervals during the 2-day fast. This did not prevent a weight loss (2.1 +/- 0.5 kg, P less than 0.01) of similar magnitude as in group A, but it restored a normal nocturnal MT secretion. The fact that glucose supplementation during fasting returns a decreased MT secretion to normal suggests that human pinealocytes require a certain minimal glucose delivery to function normally.