The effects of intrathecally administered arginine-vasopressin (AVP) and substance P (SP) on adrenal medullary secretion of epinephrine were examined in anesthetized Sprague-Dawley rats. Plasma epinephrine levels were measured in blood samples taken directly from the adrenal vein using a novel micropuncture technique. The blood samples (20-30 microliter in volume) were taken before, and 2 min, 15 min and 30 min after intrathecal injections of AVP, SP or vehicle only. Plasma was assayed for epinephrine using high pressure liquid chromatography. Adrenal venous epinephrine levels were not significantly altered by the intrathecal administration of AVP, thereby suggesting that adrenal epinephrine secretion is not involved in the cardiovascular responses previously reported to occur following similar doses of intrathecal AVP. Intrathecal SP administration, while causing blood pressure responses similar to those produced by AVP, resulted in significant increases in adrenal vein epinephrine. This finding suggests that activation of adrenal secretion of epinephrine may contribute to SP-initiated blood pressure changes.