Smoking habit did not affect the disposition kinetics of l.v. administered phenytoin. Phenytoin was given to 8 human smokers and 8 nonsmokers and plasma concentrations of phenytoin were determined over 3 day period by GLC and radioimmunoassay techniques. Nonlinear least squares computer fit of the plasma concentration-time data yielded coefficients of a biexponential equation for calculation of half-lives (t1/2.beta.), clearances (ClB) and volumes of distribution. There were no statistically significant differences in these parameters with respect to sex or smoking habit. More variable t1/2.beta. t1/2.beta. were noted in the smoking group. No differences in serum protein binding between smoking and nonsmoking groups were found. Serum thiocyanate concentrations were used as a measure of smoking habit. There was no significant correlation between thiocyanate concentrations and t1/2.beta. or ClB. Attempts to correlate phenytoin ClB with basal metabolic rate failed.