Intracellular recordings, dye-labeling and immunocytochemistry were performed in arcuate and cell-poor zone (ARC-CPZ) neurons in hypothalamic slices obtained from cycling, female guinea pigs. The hypothalamic slices were perfused with artificial medium for 9-10 hours during which time intracellular recordings were made through procion yellow electrodes and KC1/KCitrate-filled electrodes. 17 beta-Estradiol (E2) in concentrations of 10(-9) to 10(-8) M hyperpolarized and/or inhibited the spontaneous activity of 42 out of 102 ARC-CPZ neurons. Following the electrophysiological recording, procion yellow was injected in most of the recorded cells and all of the hypothalamic slices were processed immunocytochemically for LHRH. Densely stained LHRH cell bodies and fibers were widely distributed in the mediobasal hypothalamic region. Of the 42 E2-responsive neurons recorded, four contained immunoreactive luteinizing hormone-releasing hormone. These studies show that the hypothalamic slice preparation can be utilized to study the electrophysiology of ARC-CPZ neurons. Moreover, ARC-CPZ neurons and in particular, ARC-CPZ LHRH neurons in the female guinea pig are a site of rapid membrane effects of estrogen, which may be related to the negative feedback actions of estrogen on gonadotropin secretion.