Adult guinea-pigs were injected with doses of capsaicin increasing from 10 mg/kg to 400 mg/kg over 6 days. The guinea-pigs were supplied with indwelling arterial cannulae 14 days later and the next day cardiovascular function was assessed in the conscious animals. Resting blood pressures and heart rates were recorded and then baroreceptor reflex function was evaluated by recording the changes in heart period which were evoked by blood pressure responses to injections of phenylephrine and glyceryl trinitrate. Substance P was measured by radioimmunoassay and its localization examined by immunohistochemistry. The capsaicin treatment caused a substantial reduction in substance P levels in vascular and cardiac nerves. However, there were no changes in resting heart rate, blood pressure or baroreceptor sensitivity. It is concluded that the widespread substance P nerves associated with the heart and blood vessels are not necessary for baroreceptor reflex function. Their role or roles remain unknown.