In healthy human subjects the immediate responses of pulse interval and the steady-state responses of arterial blood pressure and cardiac output to changes in carotid sinus transmural pressure were determined before and during the application of a subatmospheric pressure to the lower part of the body. Increases in carotid sinus transmural pressure, effected by applications of subatmospheric pressure to the neck (neck suction) resulted in prolongation of pulse interval and decrease in blood pressure; opposite responses were obtained to application of a positive pressure (neck pressure). Application of lower body negative pressure resulted in a decrease in pulse interval (heart rate increase) but little change in blood pressure. During lower body negative pressure, the responses of pulse interval to neck pressure were reduced but those to neck suction were unaffected; the responses of blood pressure to neck suction were enhanced but those to neck pressure were unaffected. From experiments in which cardiac output was also determined, it was seen that lower body negative pressure reduced cardiac output, increased calculated total body vascular resistance and augmented the resistance response to neck suction although not to neck pressure. These results are compatible with the view that application of lower body negative pressure does not change the sensitivity of the baroreceptor reflex and that the changes in the responses are due to non-linearities of the stimulus-response curves.