In anesthetized cats, responses of single neurosecretory neurons of the supraoptic nucleus to activation of muscle receptors were investigated. Electrical stimulation (1-3 pulses at 200 Hz) of group m and IV pure muscle afferents (gastrocnemius nerve) evoked excitation of >50% of supraoptic nucleus neurons (n = 50), whereas stimulation of group Ia or lb fibers was ineffective. Baroreceptor stimulation inhibited 95% of these supraoptic nucleus neurons that responded to activation of muscle afferents. Excitation of receptors in the gastrocnemius muscle by intra-arterial injection of chemi (NaCl, KCI, and bradykinin) increased firing rates of most (84%, 74%, and 80%, respectively) neurosecretary neurons. The magnitude of the excitatory response was dose dependent-bradykinin being the most effective. The response disappeared after muscle denervation. When the gastrocnemius muscle alone was contracted phasically by ventral root stimulation, discharges of the supraoptic nucleus neurons increased, whereas quick stretch of the muscle had no effect. We conclude that activation of muscle receptors by chemical or mechanical stimulus can directly excite neurosecretory neurons in the supraoptic nucleus and that afferent impulses are carried by polymodal fibers of small diameter but not by the largest afferents (group I) from the muscle. The results may relate to increased concentrations of plasma vasopressin during exercise.Physical exercise is accompanied by antidiuresis and increased plasma level of vasopressin (1-7) as well as by respiratory and cardiovascular changes (8-12). It has been suggested that these autonomic responses do not result from secondary changes induced by increases in blood volume, core temperature, or metabolic rate during exercise but result, instead, from direct excitatory neural input from polymodal receptors in the muscle to the autonomic centers (10, 11). We showed previously that the neurosecretory neurons in the supraoptic nucleus (SON) ofthe hypothalamus were affected by excitation of peripheral somatic as well as visceral afferents (13). Thus, the increased level of plasma vasopressin could also be due to activation of polymodal receptors in striated muscle.The present investigation was done for two purposes: (i) to study characteristics of afferent fibers from the muscle that excite neurosecretory neurons in the SON and (ii) (Nembutal, 35 mg/kg). Supplemental doses of the same anesthetic agents or sodium thiopental (Pentothal, 2-5 mg/kg) were given i.v. whenever necessary. No muscle relaxant was used. A trachea cannula was inserted, and the femoral artery and vein were cannulated for blood pressure recording and fluid or drug administration. Pneumothorax and artificial ventilation was used whenever necessary to minimize movement of brain tissues. The rectal or esophageal temperature was maintained between 37-38TC by a heating pad and an overhead lamp. The animal was placed in a stereotaxic head holder and hemispherectomy was done by the method described (15). The exposed surface...