Animal studies suggest that opioids inhibit the firing rate of vestibular neurons, which are important in mediating the vestibulosympathetic reflex. Furthermore, this inhibition appears to be greater in more mature rats. In the present study we tested the hypotheses in humans that opioids inhibit the vestibulosympathetic reflex and that endogenous opioids contribute to the age-related impairment in the vestibulosympathetic reflex. These hypotheses were tested by measuring muscle sympathetic nerve activity (MSNA), arterial blood pressure, and heart rate responses to otolith organ engagement during head-down rotation (HDR) in young (24±2 years old) and older (63±2) subjects before and after administration of either an opioid receptor antagonist (16 mg naloxone in 9 young and 8 older subjects) or an opioid receptor agonist (60 mg codeine in 7 young and 7 older subjects). Naloxone did not augment the reflex increase in MSNA during HDR in young (7±2 vs. 4±2 bursts/min and 81±23% vs. 60±24% change in burst frequency and total MSNA before and after naloxone, respectively) or older subjects (2±2 vs. 1±2 burst/min and 8±7% vs. 8±9% before and after naloxone). Similarly, codeine did not attenuate the increase in MSNA during HDR in young (8±1 vs. 7±2 bursts/min and 53±4% vs. 64±16% before and after codeine) or older subjects (6±4 vs. 3±3 bursts/min and 38±21% vs. 33±20%). Mean arterial pressure and heart rate responses to HDR were not altered by either naloxone or codeine. These data do not support the concept that opioids modulate the vestibulosympathetic reflex in humans.