To examine the plausibility of the hypothesis that smoking a cigarette after a meal is motivated by accelerated metabolism of nicotine, we studied the influence of a high-protein meal on the disposition of nicotine in seven healthy smokers. Indocyanine green clearance, an estimate of hepatic blood flow, increased 31%, 50 minutes after the test meal. Consuming the meal during a steady state infusion of nicotine resulted in a small (18%) but consistent decrease in blood levels of nicotine. Our data demonstrate that food accelerates the metabolism of nicotine, but the time course and magnitude of the decline in levels of nicotine suggest that altered disposition of nicotine is not the primary motivation for smoking after meals.