In order to elucidate the role of substance P (SP) in emetic responses, effects of resiniferatoxin (RTX), an ultra-potent capsaicin analogue that releases SP, were investigated in Suncus murinus. RTX induced dose-dependent emesis, and beside vomiting, flat down, increase of respiration rate, tremor and eye twitch were notable behavioral changes at a dose of 100 μg/kg. These effects were transient, and animals became normal 30 to 40 min after the injection. RTX-induced emesis was blocked by 30 mg/kg CP-99, 994 and 10 mg/kg ruthenium red. RTX also showed anti-emetic effects. Animals treated with RTX did not respond to cisplatin, copper sulfate, nicotine nor motion after one hour. The anti-emetic effects of RTX were also inhibited by ruthenium red but not by CP-99, 994. Both emetic and anti-emetic effects of RTX were apparently desensitized. Neonatal treatment with capsaicin completely prevented emetic response to RTX but not to cisplatin, copper sulfate, nicotine and motion. RTX significantly decreased the content of SP in the nucleus tractus spinalis nerve trigemini, the dorsal spinal cord but not in the dorsal vagal complex that is considered as part of emetic pattern generator. These results suggest that SP is involved in emetic responses but its action is complicated.