Data from adults enrolled in a general population study in Tucson, Arizona, indicated that smokers have higher serum IgE concentrations than nonsmokers, despite a lower rate of allergy skin test reactivity, at least after 35 yr of age. After 15 yr of age there was a significant decline in serum IgE with age in both allergy skin test positive and skin test negative nonsmokers but no significant age decline was noted in similar groups of smokers. Ex-smokers showed a decline in serum IgE concentrations since quitting cigarettes. Also, the marked increase in geometric mean IgE that was seen in nonsmokers during the spring was not observed in smokers. The data suggested that smoking leads, directly or indirectly, to an increase in serum IgE and that this excess IgE may be qualitatively different from that seen in nonsmokers. Possible mechanisms for the effect are discussed. The observations raised the possibility that some of the adverse health effects of smoking might be immunologically mediated.