Several epidemiological studies have indicated that there may be an inverse relationship between smoking and Parkinson's disease. The purpose of this study was to determine whether chronic exposure to cigarette smoke alters the parkinsonian-like neurochemical changes caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Following 4 weeks of brief, intermittent exposure to smoke, mice were treated with MPTP, 10 mg/kg. Smoke exposure was found to reduce the decrease in striatal dopamine and metabolite levels caused by MPTP. Although smoke exposure inhibited cerebral MAO-B activity, tissues from smoke-treated mice were able to metabolize MPTP in a normal fashion. This suggests that inhibition of cerebral MAO may not be a major mechanism for the apparent protective effect of cigarette smoke.