Basal and electrical stimulation-induced release of tritiated norepinephrine (3H-NE) was determined in superfused slices of the rat hypothalamus and hippocampus. Isoproterenol (0.1-10 nM), a nonselective beta-adrenergic agonist, enhanced stimulation-evoked release of 3H-NE from hypothalamic and hippocampal slices in a concentration-dependent manner without consistently altering basal release. Isoproterenol (1 nM) increased ratios of S2/S1 to 143 +/- 4% (hypothalamus) and 152 +/- 15% (hippocampus) of control values. The facilitatory effects of isoproterenol were antagonized by propranolol (50 nM), a nonselective beta-adrenergic antagonist. The beta 2-selective adrenergic agonist clenbuterol (10-100 microM) enhanced basal release of 3H-NE in a concentration-dependent fashion. These results provide evidence for a beta-adrenergic receptor mediated regulation of NE release from hypothalamic and hippocampal slices. Whether the positive feedback mechanism contributes to any of the NE-mediated physiological functions associated with the hypothalamus and hippocampus requires further study. However, the effect of clenbuterol indicates that some of its behavioral actions in animals may be attributed to this NE release-enhancing effect observed in the present study.