Somatostatin, a peptide distributed widely throughout the gut, inhibits a variety of gastrointestinal functions. We previously reported that fasting for 48 h increased gastric somatostatin peptide and mRNA content. Thus, somatostatin could contribute to the inhibition of gastric G cells during fasting. To investigate the effect of fasting on intestinal somatostatin, we determined tissue somatostatin concentration by radioimmunoassay, somatostatin mRNA expression by Northern analysis and reverse transcription polymerase chain reaction (RT-PCR), and mRNA expression for somatostatin receptor subtypes (sst) 1-5 by RT-PCR in ileum and colon of rats either freely fed or food-deprived for 48 h. In the colon, fasting increased somatostatin concentration, somatostatin mRNA expression, and mRNA expression for two receptor subtypes (sst2 and sst3). In the ileum, no change of somatostatin peptide concentration and receptor subtype mRNA expression was demonstrated; only somatostatin mRNA expression was augmented by fasting. These results suggest that in rat colon, fasting for 48 h increases somatostatin synthesis and receptor subtype expression. These changes may be important in maintaining homeostasis during starvation.