BACKGROUND: Evidence that demonstrates the harmful effect of cigarette smoking during young adulthood is limited. Therefore, we assessed associations between cigarette smoking and several self-reported illnesses in a prospective cohort study in healthy young adults. METHODS: Data were derived from 4472 adults aged 18 to 30 years at baseline participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study and reexamined at least once after 7, 10, or 15 years. RESULTS: Cigarette smoking in 1985-86 was related to self-reported smoking-related cancers, circulatory disease, and peptic ulcer. Incidence of these diseases was 9.3/1000 person years among current smokers vs. 4.5/1000 person years among never smokers with no exposure to passive smoke, relative risk (adjusted for race, sex, education, and center) 1.96 (1.42-2.70). Assuming causal relationships, 32% of these premature incidents were attributable to smoking. The relative risks of liver disease, migraine headache, depression, being ill the day before the examination, and chronic cough and phlegm production were also higher in smokers. CONCLUSIONS: Smokers aged 18-30 followed for 7 to 15 years reported an excess of both major and minor ailments related to earlier and current smoking. Thus, prevention, cessation, and avoiding passive smoking should remain strong goals among young people.