In the rat, hypoglycaemia inhibits growth hormone secretion, but the mechanism is unclear. To investigate this further, we have studied the effects of glucose and 2-deoxy-D-glucose on somatostatin and LHRH release from rat hypothalamic fragments incubated in vitro. Glucose (1.35–22 m M) was added to glucose-free medium and 5 and 50 m M 2-deoxy-D-glucose were added to medium containing 5.5 m M glucose. Medium somatostatin and LHRH levels were measured by RIA. Somatostatin and LHRH released diluted in parallel with synthetic somatostatin and LHRH. Sephadex gel filtration demonstrated two molecular forms of somatostatin, 70% coeluting with somatostatin-14 and 30% with somatostatin-28; LHRH coeluted with synthetic LHRH. KC1 (30–100 m M) resulted in release of somatostatin and LHRH; this was reduced in calcium-free medium. Basal and K<sup>+</sup>-stimulated somatostatin release were significantly increased by reducing glucose levels (r = -0.6, p < 0.001). Basal LHRH was not influenced by glucose. Basal and K<sup>+</sup>-induced somatostatin release were significantly increased by 2-deoxy-D-glucose (p < 0.05), while LHRH levels remained unchanged. Our results demonstrate that basal and K<sup>+</sup>-induced somatostatin release from rat hypothalamic fragments are modulated by local glucose concentrations, and this effect is specific as it is not paralleled by LHRH changes. We suggest that the reduction in growth hormone secretion during hypoglycaemia in the rat might be mediated, at least in part, via a direct effect of glucose on somatostatin release.