Rabbit nasal olfactory and respiratory microsomes demonstrate high activity toward [3H]-(S)-nicotine, with specific activities of 22.2 and 6.5 nmol/min/mg protein, respectively. The major metabolite produced is (S)-nicotine delta 1'; 5'-iminium ion, with lesser amounts of nornicotine and the N'-oxide. Reconstitution of the rabbit nasal microsomal system with cytochromes P-450 NMa and NMb indicated that only P-450 NMa has significant activity toward nicotine, and the metabolite profile and turnover are similar to that observed with nasal microsomes. The low Km (35 microMs) and high Vmax (28 min-1) suggest that a significant portion of inhaled nicotine is metabolized by nasal tissues in the rabbit.