The threshold pressure of single baroreceptor units is decreased after compared with before exposure to pulsatile pressure according to previous studies in our laboratory. The purpose of the present study is to characterize the determinants of sensitization of arterial baroreceptors by pulsatile pressure. Carotid sinus nerve activity was recorded in dogs anesthetized with chloralose. Two indexes of baroreceptor "sensitivity" were obtained by comparing nerve activity before and immediately after exposure of the isolated carotid sinus to pulsatile pressure for periods up to 10 minutes. Sensitization occurred 1) when the threshold pressure of single baroreceptor units determined with a slow nonpulsatile ramp decreased after as compared with before pulsing and 2) when multiple unit activity increased after as compared with before pulsing at various mean levels of static pressure. Sensitization was evident after pulsing at mean pressures of 50 and 100 mm Hg, but not at 150 and 200 mm Hg, and was caused by the pulsatile change in diameter or deformation and not by the pulsatile change in wall tension. The magnitude of the effect was directly related to the duration of the pulsing period and to the frequency and amplitude of the pressure pulses. The sensitization could not be explained by increased diameter (sonomicrometers) or strain of the carotid sinus at the same pressure after pulsing; thus, there was an increase in "strain sensitivity" that outlasted the period of pulsing by up to several minutes. In most experiments the shift from static to pulsatile pressure at 50 and 100 mm Hg caused an increase in nerve activity, yet sensitization occurred after pulsing when one would have expected postexcitatory hyperpolarization or depression of activity upon return to static pressure. The sensitization was not caused by the release of prostacyclin from the endothelium since it was not reduced after endothelial denudation or inhibition of cyclooxygenase with indomethacin (30–80 μM) or ibuprofen (250 μM}. We speculate that sensitization of baroreceptors by pulsatile pressure may contribute to the decreased sympathetic activity after periods of elevated pulse pressure (e.g., after exercise). We also propose that the decreased sensitivity of baroreceptors after acute elevation of arterial pressure (acute resetting) may be offset in part by the sensitizing effect of increased pulsatile stretch.