Clinical effects of spa therapy were examined in 60 elderly asthmatics in comparison between ex-smokers with a long history of cigarette smoking more than 20 years and never-smokers. Spa therapy wse effective in 47 of the 60 subjects (78.4%) with asthma. Ragarding in influence of cigarette smoking, the therapy was effective in 16 of the 24 astmatics (66.7%) with a long history of cigarette smoking. In con-trast, the therapy was effective in 31 of the 36 asthmatics (86.1%) withput smoking history. The spa efficacy was significantly larger in asthmatics without smoking history than those with (P<0.05). There was no significant correlation between spa efficacy and IgE-mediated reactions. Bronchial hyperresponsiveness was significantly higher in subjects with slight or no efficacy of spa therapy than in those with marked and mod-erate efficacy both in ex-smokers and never-smokers as well as in total subjects. The generation of leukotriene B4 (LTB4) by leucocytes was significantly increased in sub-jects with slight or no efficacy of spa therapy than in those with marked and moderate efficacy in total subjects and in those with smoking history, but not in those without smoking history. The generation of leukotriene C4 (LTC4) by leucocytes was not sig-nificantly correlated with spa efficacy in total subjects, and also either in ex-smokers or never-smokers. The results demonstrate that clinical effects of spa therapy are in-fluenced by long-term cigarette smoking, which increases bronchial hyperrespon-siveness and the generation of LTB4 by leucocytes.