Cardiovascular and sympatho-adrenomedullary responsiveness at rest and during stress were studied in weight-matched, sexually mature male and female rats. At rest, although there were no sex differences in cardiovascular parameters, females had two-fold higher plasma levels of norepinephrine (NE) and epinephrine. Resting plasma levels of neuropeptide Y-immunoreactivity (NPY-ir, a putative sympathetic cotransmitter and a vasoconstrictor) were similar in both sexes. Stresses of handling and cold (4-degrees-C) water exposure induced greater pressor and tachycardiac responses in males than in females. Males but not females exhibited a protracted recovery from the stress-induced pressor responses and a 2-fold increase in plasma NPY-ir suggesting that NPY release is sexually differentiated. Only in males, low basal plasma NE and NPY-ir levels inversely correlated with greater cold-induced pressor responses. Furthermore, in areflexic pithed rats, pressor adrenergic and NPY responses were greater in males than in females suggesting the possibility of "down"-regulation of vascular adrenergic receptors in females (due to elevated circulating catecholamines) and "up"-regulation of NPY and adrenergic receptors in males.