We have studied the effects of starvation and of obesity on somatostatin, insulin, and glucagon release from an isolated perfused organ system in fed and 3- and 5-day fasted Holtzman rats and in obese (fa/fa) and lean (Fa/?) Zucker rats. Fasting for 3 days significantly decreased basal (-71%) and amino acid-stimulated (-62%) somatostatin output. After 5 days of starvation, there was a significant increase over the 3-day level in somatostatin output stimulated by amino acid plus glucose (+540%) and by amino acids plus tolbutamide (+238%). Three and five days of starvation severely depressed insulin output while having no statistically significant effects on glucagon secretion. Somatostatin output from obese Zucker rats was significantly greater than that from lean controls in response to amino acids (41.2 +/- 13.2 vs. 16.3 +/- 10.3 ng/25 min, P less than 0.05). Insulin output was greatly increased from obese compared to lean Zucker rats, whereas there were no statistically significant differences in glucagon output. These data show that fasting decreases and obesity increases both somatostatin and insulin release. They suggest that altered stimulation by nutrients was primarily responsible for changes in somatostatin and insulin release observed in starving and obese rats.