In the rat, it has been proposed that angiotensin II (AII) neurons in the subfornical organ, a midline circumventricular structure, participate in the activation of hypothalamic neurosecretory neurons and promote a rise in plasma vasopressin and oxytocin. In this study, we observed AII-immunoreactive fibers coursing throughout the supraoptic nucleus as well as in other magnocellular cell groups of the hypothalamus. Moreover, following retrograde transport of Fast blue deposited within the supraoptic nucleus, cell counts in our best case revealed that 40% of AII-immunoreactive neurons in subfornical organ contained Fast blue, and 46% of the retrogradely labeled subfornical organ cells contained AII. In separate electrophysiological studies, post-stimulus histograms from 18 of 28 supraoptic neurons displayed a 30-55% reversible reduction in the excitation evoked by an electrical stimulus in the subfornical organ during local pressure applications of 100 microM to 1 mM saralasin. In 2 of 14 other cells, tubocurare (100 microM) produced only a 10% reduction in subfornical organ excitation. These observations indicate that AII may mediate an excitatory input to supraoptic neurons from the subfornical organ.