The rate of smoking was significantly reduced in volunteer subjects by providing effective nicotine replacement, self-help material, and weekly visits with a nurse for 6 weeks. Nicotine-replacement therapy with a transdermal nicotine patch (Nicolan) almost doubled the 6-week smoking-cessation rate in comparison with that in a placebo group (77% versus 39%; P = 0.002) among subjects who were smoking at least 20 cigarettes per day at baseline. Although most subjects who used the active nicotine patches had skin reactions, the reactions were primarily mild. For use of both active and placebo patches, the level of patient compliance was high. Among subjects who continued to smoke, the use of cigarettes was decreased to less than 50% of the baseline smoking level in 7 of 7 with active nicotine patches and in 15 of 19 with placebo patches. Outcomes beyond 6 weeks showed a substantial relapse rate in both groups. Thus, when nicotine-replacement therapy is provided, a need exists for concurrent behavioral intervention and training for prevention of a relapse, neither of which was part of this protocol.