BACKGROUND: Capsaicin-sensitive afferents have been implicated in the control of visceral sensorimotor functions. AIM: To study the effects of capsaicin on the sensorimotor function of the proximal stomach in humans. METHODS: In 10 healthy subjects, a gastric barostat was used to study the effect of saline or capsaicin-containing red pepper sauce on the sensitivity to gastric distension and on gastric accommodation to a meal. RESULTS: The administration of capsaicin was accompanied by a relaxation of the proximal stomach. After capsaicin, the compliance of the proximal stomach was increased and higher perception scores were reached for the same distending pressures. Dosing with capsaicin significantly decreased the pressures and corresponding wall tensions at the discomfort threshold. Gastric accommodation to a meal was not altered by capsaicin. CONCLUSION: The acute administration of capsaicin decreases proximal gastric tone, inhibits phasic contractility of the proximal stomach and increases sensitivity to proximal gastric distension. These data suggest the involvement of vanilloid receptor 1 in the modulation of gastric sensorimotor function in humans.