Smoking habit did not affect the disposition kinetics of intravenously administered phenytoin. Phenyoin was given to 8 smokers and 8 nonsmokers and plasma concentrations of phenytoin were determined over a three day period by GLC and RIA techniques. Nonlinear least squares computer fit of the plasma concentration-time data yielded coefficients of a biexponential equation for calculation of half-lives (t1/2beta), clearances (ClB) and volumes of distribution. There were no statistically significant differences in these parameters with respect to either sex or smoking habit. However, more variable t1/2beta's 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 t1/2beta or ClB. Attemps to correlate phenytoin ClB with basal metabolic rate also failed.