Unloading of the baroreceptors due to orthostatic stress increases corticospinal excitability. The purpose of this study was to examine the effects of baroreceptor unloading due to orthostatic stress on intracortical excitatory and inhibitory pathways in the motor cortex. With transcranial magnetic stimulation, measures of intracortical excitability for a hand muscle were tested on 2 days in healthy young adults. Lower body negative pressure (LBNP) of 40 mmHg was applied during one of the days and not during the Control day. During application of LBNP heart rate and the low-frequency component of heart rate variability increased, while mean arterial blood pressure was maintained. In the resting state, LBNP decreased short-interval intracortical inhibition (SICI) and had no effect on intracortical facilitation (ICF) or short-interval intracortical facilitation (SICF) compared with the Control day. During isometric contraction, no effects of LBNP were observed on tested measures of intracortical excitability including SICI, SICF, and cortical silent period. It was concluded that baroreceptor unloading due to orthostatic stress results in diminished intracortical inhibition, at least in the resting muscle. © 2014 the American Physiological Society.