Many smokers are unable to use gum as a cessation aid due to fillings, bridgework and dyspepsia or they reject it for esthetic reasons. The nicotine sublingual tablet is a new alternative to the nicotine polacrilex chewing gum that does not necessitate chewing. Twenty subjects used 2-mg sublingual nicotine tablets and placebo in a double-blind randomized crossover study of 2-day smoke-free periods. Craving and other withdrawal symptoms were rated on 100-mm visual analog scales (VAS) nine times over each 2-day period. Plasma nicotine concentrations in the afternoon of each study day were determined. A blood sample was also taken in the afternoon of a 2-day period with normal smoking. The mean number of nicotine tablets was 10 and seven on days 1 and 2, respectively. The corresponding number for placebo tablets was six and five. No subject used less than five tablets on any study day. The degree of nicotine substitution, defined as the quotient between the plasma levels achieved with the sublingual tablet and smoking, was 43, 30 and 23% for smokers with FTQ ≤6, FTQ = 7 and FTQ ≥8 (Fagerstroöm Tolerance Questionnaire), respectively. Active treatment was significantly superior in decreasing craving and other withdrawal symptom scores compared to placebo treatment. Mean total scores were reduced by approximately 50%. Adverse events were mainly symptoms of local irritation such as a burning sensation in the throat or under the tongue, a lump in the throat and heartburn. These results demonstrate partial relief of the tobacco withdrawal syndrome with use of the sublingual tablet similar to that achieved from other forms of nicotine replacement.