The goal of our study was to develop a simple and practical method for simulating diving in humans using facial cold exposure and apnea stimuli to measure neural and circulatory responses during the stimulated diving reflex. We hypothesized that responses to simultaneous facial cold exposure and apnea (simulated diving) would be synergistic, exceeding the sum of responses to individual stimuli. We studied 56 volunteers (24 female and 32 male), average age of 39 years. All subjects were healthy, free of cardiovascular and other diseases, and on no medications. Although muscle sympathetic nerve activity (MSNA), blood pressure, and vascular resistance increased markedly during both early and late phases of simulated diving, significant reductions in heart rate were observed only during the late phase. Total MSNA during simulated diving was greater than combined MSNA responses to the individual stimuli. We found that simulated diving is a powerful stimulus to sympathetic nerve traffic with significant bradycardia evident in the late phase of diving and eliciting synergistic sympathetic and parasympathetic responses. Our data provide insight into autonomic triggers that could help explain catastrophic cardiovascular events that may occur during asphyxia or swimming, such as in patients with obstructive sleep apnea or congenital long QT syndrome.