The polydipsic inbred mice, STR/N, are known to possess an extremely strong appetite for drinking but no abnormality in the vasopressin system and renal functions. In brain slice preparations the sensitivity of neurons in the anteroventral region of the third ventricle (AV3V) and the subfornical organ (SFO) to angiotensin II (ANG II) was investigated using extracellular recordings in the STR/N and its control, Swiss/Webster (S/W) mice. In the AV3V, less proportion of neurons (15 out of 168; 9%) of the STR/N than that in the S/W (49/206; 24%) was excited by ANG II added to the medium. In the SFO, a proportion of neurons excited by ANG II was again lower in the STR/N (27/104; 26%) than in the S/W mice (64/118; 54%). The threshold concentration of ANG II for excitation of the AV3V and SFO neurons was, however, similar for both strains, 10(-9) M or less. Only one neuron in the SFO of a S/W mouse was inhibited by ANG II application. The excitatory effect of ANG II on AV3V and SFO neurons of both strains of mice persisted under synaptic blockade and was reversibly antagonized by an ANG II antagonist, saralasin. Such differences in sensitivity to ANG II of neurons in the SFO and AV3V, the regions thought to be involved in drinking behavior, suggest the involvement, at least in part, of the central angiotensin system in the polydipsia of the STR/N mice.