A double-blind, placebo controlled trial was undertaken to examine the effect of the 5-HT3 antagonist, ondansetron .25 mg bd on cigarette withdrawal symptoms and on proportion of individuals maintaining continuous abstinence for 4 weeks in a smoking treatment programme. A total of 111 smokers were allocated to active or placebo conditions and began taking their study medication 2 weeks before the quit date. They attended the smokers clinic for weekly group treatment sessions. The results showed no evidence for less severe withdrawal symptoms or improved abstinence rates in the active medication group. They suggest that inhibiting 5-HT3 activity is not an effective method of controlling nicotine withdrawal or helping smokers to stop.