1. Substance P, injected into a lateral brain ventricle of urethane-anaesthetized rats, caused dose-dependent increases in blood pressure and heart rate. 2. By contrast, exposure of the obex region of the medulla oblongata to pieces of filter paper soaked in substance P-containing solution resulted in falls of blood pressure and heart rate in both rats and cats. 3. A more precise application of substance P to the first synapse of the baroreceptor reflex by micro-injection into defined areas of the nucleus of the solitary tract also led to an activation of the baroreceptor reflex. 4. Capsaicin, which is known to release substance P from primary afferents, mimicked the sympatho-inhibitory and cardiovascular effects of substance P when applied locally to the nucleus of the solitary tract. 5. The results are compatible with a transmitter or neuromodulatory role for substance P at the first synapse of the baroreceptor reflex.