Effects of corticotropin-releasing factor (CRF) on paraventricular (PVN) neurons of the hypothalamus were investigated in rat brain slice preparations. Of 110 PVN neurons recorded extracellularly, bath application of 10(-7) M CRF excited 31 (28%) and inhibited 27 (25%). In 8 (7%) neurons, excitation was followed by inhibition. Five neurons tested were dose-dependently excited. To know whether these responses still remained under synaptic blockade, 10(-7) M CRF was applied to 30 PVN neurons in a low Ca2+, high Mg2+ medium. Seventeen PVN neurons were excited, but neither inhibition nor exciation followed by inhibition was observed. Of 13 intracellularly recorded PVN neurons, the membrane potential of 9 was depolarized by 10(-6) M CRF. The others were not affected. In the low Ca2+, high Mg2+ medium, the firing rates of the neurons did not decrease but increased even in neurons that decreased their firing rates in the control medium. These results suggest that CRF may excite PVN neurons directly, and depolarize the membrane potential.