Aggregating platelets release factors that act in a local paracrine manner to alter vascular tone. The purpose of the present study was to explore the possibility that factors released from aggregating platelets may alter the sensitivity of arterial baroreceptors. Baroreceptor activity was recorded from the vascularly isolated carotid sinus of rabbits anesthetized with sodium pentobarbital. The carotid sinus was filled with oxygenated Krebs-Henseleit buffer and distended with slow ramp increases in nonpulsatile pressure. Sensitivity of baroreceptors to increased pressure was determined before and during intraluminal exposure of the sinus to washed human platelets suspended in Krebs' buffer. Platelets activated with thrombin (0.4 units/ml) decreased baroreceptor activity and the slope of the pressure-activity curve significantly (n=6). The platelet-induced decrease in baroreceptor sensitivity was related to the duration of exposure to platelets with no change in baroreceptor activity after 4 minutes and a progressive decrease in activity over the next 12 minutes. The slope of the pressure-nerve activity relation averaged 1.26±0.08 %/mm Hg during control and decreased to 0.97±0.22, 0.80±0.19, and 0.53±0.15 %/mm Hg after 12–16 minutes of exposure to 107, 108, and 3–6×108activated platelets/ml, respectively (p<0.05). Baroreceptor sensitivity was restored after removal of platelets from the carotid sinus. Thrombin alone had no effect on baroreceptor sensitivity. Activated platelets did not alter the carotid pressure-diameter relation, suggesting a direct inhibitory effect on baroreceptors. The slope of the pressure-activity curve and maximum baroreceptor activity were not decreased by the stable thromboxane analogue U46619, serotonin, or ADP. We conclude that an as-yet-unidentified factor released from aggregating platelets acts in a paracrine manner to decrease baroreceptor sensitivity. We speculate that in pathological states such as atherosclerosis platelets aggregating in carotid sinuses may contribute to decreased baroreceptor sensitivity and trigger reflex sympathetic activation with potential deleterious effects (vasospasm and hypertension).