The effects of the benzodiazepines and somatostatin (SS) on learning and memory are the opposite of each other. To investigate a possible relationship between these two components, the effects of the administration over time of diazepam and of a benzodiazepine antagonist, 2-phenylpyrazolo [3,4-c]-quinolin-3(5H)-one (CGS 8216), on the levels of somatostatin-like immunoreactivity (SSLI) and on the binding of [125I]Tyr11-somatostatin were studied in the hippocampus of the Wistar rat. Diazepam (5 mg/kg/day, i.p.) and CGS 8216 (20 mg/kg/day, i.p.) did not affect SSLI in the hippocampus, at the three times studied (3, 7 or 14 days). Administration of diazepam for 3 or 7 days decreased the number of somatostatin receptors in synaptosomes from the hippocampus, without influencing their apparent affinity. This decrease could be blocked by concomitant administration of CGS 8216, whereas CGS 8216 alone had no observable effect. After 2 weeks of daily injections of diazepam the levels of binding of somatostatin in the hippocampus returned to control values, coinciding with the tolerance that develops to chronically-administered benzodiazepine agonists. These results suggest that somatostatin receptors might be regulated by benzodiazepine receptors and perhaps may also play a role in some of the behavioural effects of the benzodiazepines.