This study examines the effect of muscimol, a high affinity, specific gamma-aminobutyric acid (GABA) agonist, on glucose-stimulated somatostatin and insulin release from the isolated, perfused rat pancreas. Perfusion with low glucose (50 mg/dl) conditions resulted in basal somatostatin release of 46 ± 4 pg/ml. Basal insulin release was less than 20 μU/ml. High glucose (300 mg/dl) conditions stimulated somatostatin and insulin release. Steady-state levels of somatostatin and insulin release under high glucose conditions were 425 ± 12 pg/ml and 419 ± 18 μU/ml, respectively. Perfusion with medium containing 1 μM muscimol inhibited glucose-stimulated somatostatin release by 38%, whereas the course of glucose-stimulated insulin release was unaffected. Tentative conclusions from this study are (1) that GABA is potentially a modulator of islet somatostatin but not insulin release, and (2) the fact that somatostatin, an inhibitor of insulin, can be suppressed 38% without coincidental increase in insulin release seems to indicate that, under high glucose conditions, somatostatin is without a significant paracrine effect on the beta-cells.