BACKGROUND: The objective of this longitudinal study was to assess the association between major depression and heart complaints in a population of young and healthy adults. METHODS: Starting at the age 20/21, participants of the Zurich Study underwent 6 structured, psychological interviews during a span of 20 years. We evaluated longitudinal data from 277 persons who participated in all 6 interviews including questions about heart complaints. RESULTS: Over 20 years, heart complaints were reported by two thirds of participants, and the frequency of depression was 11.4%. At the age of 40/ 41, heart complaints were significantly associated with earlier heart complaints and major depression, both more often in women. Recurrent brief depression showed a tendency, but neither minor depression nor depressive symptoms were predictive for later heart complaints. CONCLUSIONS: This study suggests that major depression is a predictor for heart complaints at the age of 40 and that the severity of depressive disorder in younger age has an effect on subsequent heart complaints. Follow-up data will help to elucidate whether these subjective heart complaints show any correlation with a later coronary heart disease.