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·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 hard-core smokers was low. Other recycling set-ups are warranted, which might include more aggressive nicotine dosing. Eur Respir J., 1996Respir J., , 9, 1619 To attain an acceptable long-term success rate in smoking cessation, some basic principles have to be followed. The most important is that from the target quit day the smokers have to quit cigarettes completely; even a single cigarette on a few occasions ("slips") will probably lead to relapse.The role of nicotine replacement with nicotine chewing gum and transdermal patches in smoking cessation has been established through several placebo-controlled clinical trials [1,2], and a doubling of the success rate can be expected [3,4]. The dose and the duration of nicotine replacement therapy has not been fully evaluated, though a duration of 6-12 weeks is recommended in most studies, and dose-response effects have been found for nicotine gum and patch [3]. The easiest nicotine product to use is the patch; when applied to the skin it releases about 1 mg of nicotine per hour, i.e. a fixed dosing system. Nicotine nasal spray (NNS), inhaler and gum have to be used ad libitum or prescribed to be taken every hour or so, with the possibility of self-regulating the dose when needed.Trials comparing the four different nicotine formulations have not been performed. In a meta-analysis, comprising 17,703 subjects and 42 gum studies, nine patch studies, one NNS and one inhaler study, the odds rates of nicotine therapy compared with controls were 1.61 for gum, 2.07 for patch, 2.92 for NNS and 3.05 for inhaler [5]. The possible role of nasal aerosols in smoking cessation have been sparsely examined [6][7][8][9]. The NNS is the nicotine delivery system most closely like smoking cigarettes, due to the fast nicotine absorption from the nasal mucosa.In two well-designed, controlled trials of NNS, comprising 227 and 248 smokers, the 1 year outcomes were 26 and 27% in the active group compared with 10 and 15% in the placebo groups [10,11]. In one study, a nicotine substitution of 40% of the smoking l...