The circadian variations of exocrine pancreatic secretion were studied in conscious rats provided with pancreatic, biliary, duodenal, and peritoneal cannulas and kept in restraint cages under controlled conditions, with a regular 12-h light cycle. Rats were divided into fed and fasted groups, and experiments were performed separately. During a 4-day post-surgical recovery period, rats were fed ad libitum. During the experiment, fed rats had free access to food and water. Food, but not water, was denied fasted rats 10 h before the experiment and for its 48-h duration. During the experiment, pancreatic juice was continuously collected for 4 and 2 days from fed and fasted rats, respectively. Every 30 min, a 20-microliters aliquot of sampled pancreatic juice was removed for total protein, amylase, and chymotrypsinogen assays. The remainder was mixed with bile collected simultaneously, and the mixture was recirculated into the duodenum. Over the 4- and 2-day periods there was a clear circadian rhythm of 24-h duration; for all measured parameters, secretory rates increased in the dark period and decreased during the light period. This major circadian rhythm was unexpectedly found to be superimposed on by a remarkably constant neurosecretory-like minor cycle of 2-h duration present in both fed and fasted states. The amplitude of the minor cycle was diminished by fasting. The outputs of fluid, total protein, and amylase were found to be only modestly correlated with each other, whereas chymotrypsinogen output was virtually completely independent of the others. The results suggest that the spontaneous major increase of exocrine pancreatic secretion in the dark was at least partially independent of food intake.(ABSTRACT TRUNCATED AT 250 WORDS)