The most severely nicotine-dependent patients who have tried traditional treatment programs without success may require maximal intervention to achieve abstinence. In the Clinical Research Center at the Mayo Clinic, we assessed the feasibility of an inpatient treatment program for 24 such subjects, who were hospitalized (in groups of 6) for 2 consecutive weeks. A combination of behavioral, chemical-dependence, and transdermal nicotine-replacement therapy was provided in a smoke-free, protected milieu. Components of the program included group therapy, management of stress, exercise, daily lectures, and supervised activities. The mean age of the 18 women and 6 men was 51.3 years (range, 29 to 69 years). The mean duration of smoking was 33.7 years, and the number of cigarettes smoked per day at the time of admission averaged 33.2. The most frequent tobacco-related medical illnesses were chronic obstructive pulmonary disease, arteriosclerosis obliterans, and coronary artery disease. All subjects but two--each smoked part of a cigarette--remained abstinent from the use of cigarettes while in the Clinical Research Center, and all completed the 2-week inpatient program. The subjects underwent follow-up for 10 weeks after dismissal and were contacted periodically thereafter. At 1 year, 7 of the 24 subjects (29%) had maintained continuous abstinence from smoking, and their self-reported status at 1 year was verified biochemically.