In anesthetized, spontaneously hypertensive rats (Okamoto-Aoki), injections of 0.75, 1.5, and 3.0 microgram/kg PGE2 into the jugular vein caused transient decreases (mean +/- SE) in arterial pressure of 21 +/- 2, 37 +/- 3, and 78 +/- 6 mmHg, respectively, before cervical vagotomy and of 1 +/- 1, 15 +/- 4, and 15 +/- 6 mmHg after cervical vagotomy. The vasodepressor effect of jugular vein injections of 3.0 microgram/kg PGE2, but not of lower doses, was depressed by vagotomy in normotensive Wistar-Kyoto and Sprague-Dawley rats. Vagotomy did not reduce the hypotensive response to intra-aortic injections of PGE2 in these hypertensive and normotensive rats. The depressor effect of PGE2 thus appears to have a significant reflex component mediated through cardiopulmonary receptors subserved by vagal afferents, with hypertensive rats exhibiting a lower threshold than normotensive rats. A vagally mediated reflex component to the depressor effect of PGE2 could not be demonstrated in normotensive rabbits or in rabbits and rats with chronic renovascular hypertension. Thus, a naturally occurring vasoactive substance can stimulate cardiopulmonary receptors subserved by vagal afferents in the rat, and spontaneously hypertensive rats appear to be especially sensitive to this effect.