We compared the pharmacokinetic profiles of the highest marketed doses of three different patch systems using a crossover study design. Specifically, each of the 25 subjects was assigned to receive the Pharmacia-Upjohn (McNeil) 15-mg, 16-h patch, the Novartis 21-mg, 24-h patch, and the Alza (SmithKline Beecham) 21-mg, 24-h patch. Subjects used each patch for 3 consecutive days, applying a new patch each morning. Plasma nicotine concentrations were measured 15 times during the first 24-h period and at 48, 48.5, 49.5, and 51 h following initial patch application. Measures of total nicotine absorbed (AUC), maximum plasma nicotine concentration (C(max)) and minimum plasma nicotine concentration (C(min)), were higher for the 21-mg, 24-h patches than for the 15-mg, 16-h patch during both the first day of dosing and during the modeled steady-state period (48-72 h after initial application). Within the 21-mg, 24-h patch systems, the Alza patch produced significantly higher AUC and C(max) values during acute dosing and during steady state, but there was no difference between C(min) values. The time to reach C(max) (T(max)) was fastest for the Alza patch system; the Pharmacia-Upjohn patch produced a faster T(max) than the Novartis patch. These results indicate that there are significant differences between the pharmacokinetics of the currently marketed patch systems, which may be important for effective relief of withdrawal symptoms and cigarette craving.