This study was done to determine whether there were any differences in subjective symptoms of opiate withdrawal or methadone pharmacodynamics among patients as they were switched between three different oral formulations of methadone. Patients enrolled in a three-way double-blind crossover trial of three methadone formulations. Subjective symptoms and pharmacodynamic measures were assessed throughout the study period. Eighteen patients were enrolled the study. No statistically significant differences in any of the pharmacodynamic parameters studied were found among the three methadone preparations. There was no significant difference among preparations in the rate and extent of rise and fall in plasma methadone levels during a 24-hour intensive sampling period. Subjective symptoms also did not correlate with methadone formulation. Intolerance to changes in methadone formulation, often observed clinically, do not appear to have a pharmacodynamic basis. Our findings support the notion that such change intolerance reflects factors other than the pharmacologic properties of the different formulations of methadone.