Somatostatin-like immunoreactivity was localized in nerves in whole mount preparations of the separated layers of the guinea-pig intestine. The directions in which the neurons project were determined by examining the accumulation of somatostatin-like immunoreactivity after axonal flow was interrupted. In some experiments this was done by crushing or cutting the nerves in isolated preparations which were then maintained in oxygenated Krebs solution for 3-5 h. In other experiments, the nerves were cut in vivo and the animals allowed to survive for 4-8 days before the intestine was examined. Somatostatin immunoreactive nerve cell bodies were found in both the myenteric plexus, where they represented 4.7% of the total population of neurons, and in the submucous plexus, where they formed 17.4% of the total population. The axons of the somatostatin-containing neurons in the submucosa are not polarized while those of the somatostatin-containing neurons in the myenteric plexus of the small intestine project in the anal direction for 8-12 mm to form pericellular baskets around other enteric neurons, some of which are reactive for somatostatin. It is postulated that somatostatin-containing neurons in the myenteric plexus are interneurons in a descending nerve pathway, possibly the one involved in the descending inhibitory reflex of peristalsis.