The effects of transedermal nicotine on acute physiologic, performance and subjective measures of tobacco withdrawal were evaluated in a residential, double-blind, placebo-controlled, crossover study. Ten subjects smoked ad libitum for 4 days and underwent monitored tobacco abstinence for 3 days. On no-smoking days, three transdermal nicotine delivery systems (patches) that delivered a total of 0, 10, 20 or 30 mg of nicotine were applied for 16 hr. Experimental measures were collected 6 hr after the application of the patches. Plasma levels of nicotine and cotinine indicated that the 20- and 30-mg treatment condition fully replaced the nicotine ordinarily obtained from smoking. During nicotine abstinence (0 mg condition) typical signs of tobacco withdrawal were evident including: decreases in pulse rate, increases in electroencephalographic theta power, increases in subjective measures of tobacco abstinence and slowed performance on computer-delivered cognitive tests. Nicotine patch treatment diminished the physiologic and performance changes, but subjective measures of tobacco abstinence (cigarette craving, increases in withdrawal scores) were not significantly reduced. These data indicate that the nicotine patch may be used to diminish aspects of tobacco abstinence that could affect performance even though withdrawal discomfort may persist.