The hippocampi of species commonly used for in vitro physiologic studies were examined to determine if there were species-specific and regional differences in somatostatin immunoreactivity. The distributions of somatostatin-immunoreactive somata and fiber plexuses were determined, and the concentration of somatostatin along the septotemporal axis of the hippocampus was measured using a radioimmunoassay. There are many similarities in the patterns of somatostatin immunoreactivity in the hippocampi of mice, rats, guinea pigs, and rabbits. All species had a relatively even distribution of somatostatin-positive perikarya across three fields of the hippocampus (dentate gyrus, CA3, and CA1-2), a similar distribution of somatostatin-immunoreactive perikarya across the strata of the CA1-2 field and the dentate gyrus; and more somatostatin-positive cells in temporal than in septal hippocampus. However, there are species-specific differences in the distribution of somatostatin-immunoreactive perikarya across the strata of CA3. In addition, unlike the other species examined, mice appeared not to have a somatostatin-immunoreactive fiber plexus in the molecular layer of the dentate gyrus. The functional significance of these differences remains to be determined.