A possible role of substance P-containing nerves in the contractile response to nicotine was investigated in isolated rabbit bronchial smooth muscle preparation. 2. Nicotine caused a contraction which was attributed to the release of acetylcholine in the rabbit bronchus. The response was reduced by capsaicin (10(-5) M) and a substance P antagonist, [D-Arg1, D-Pro2, D-Trp7.9, Leu11] substance P (10(-5) M). 3. Substance P (10(-7) M)-induced contraction was reduced by atropine (10(-6) M) and potentiated by physostigmine (10(-6) M). Furthermore, substance P (10-7 M) enhanced the release of tritium or acetylcholine from the [3H]choline labelled bronchi. 4. Results suggest that substance P-like tachykinin accelerates the nicotine-evoked prejunctional endogenous neural release of acetylcholine on the nervous cells in the rabbit bronchial preparation.