The primary aim of this smoking cessation study was to evaluate the effect of long-term treatment with nicotine nasal spray in a group of hard-core smokers. A further aim was to compare the effect of ad libitum with fixed dosage of nasal nicotine spray. Eighty nine smokers, failures from two earlier studies with nicotine patches, were enrolled in an open smoking cessation study with nicotine nasal sprays, to be used ad libitum (n=45) or on a fixed schedule of 1 mg x h-1 during the day (n= 44). Carbon monoxide-verified continuous abstinence from smoking beyond Week 2, was 39% at 3 weeks, 12% at 3 months, 10% at 6 months and 6% after 1 yr, with no significant difference in success rate between ad libitum and fixed dosing. Mean daily nicotine dose was 15-16 mg during the first 3 months (range 2-65 mg). Tolerance to local irritating side-effects of nicotine developed during the first weeks of use. Although short-term outcome was promising, the long-term success rate in this group of hardcore smokers was low. Other recycling set-ups are warranted, which might include more aggressive nicotine dosing.