The role of stressful life events in the onset of Graves' disease (toxic diffuse goitre) is controversial. However, the numerous early clinical reports that supported such an association were not adequately controlled and specificity of the diagnosis could be questioned. Later studies have not shown a causal relation, but these studies were small, did not have proper controls, or epidemiological methods were inappropriate. To assess possible associations between life events, heredity, social support, and Graves' disease, we have done a population-based case-control study in a defined area with about 1 million inhabitants. Over 2 years, 208 (95%) of 219 eligible patients with newly-diagnosed Graves' disease and 372 (80%) of all selected matched controls answered an identical mailed questionnaire about marital status, occupation, drinking and smoking habits, physical activity, familial occurrence of thyroid disease, life events, social support, and personality. Compared with controls, patients claimed to have had more negative life events in the 12 months preceding the diagnosis, and negative life-event scores were also significantly higher (odds ratio 6.3, 95% confidence interval 2.7-14.7, for the category with the highest negative score). Individuals who had relatives with thyroid disease (especially first-degree and second-degree relatives) were more likely to have Graves' disease (3.6, 2.2-5.9). Slightly more patients than controls were divorced (1.8, 1.0-3.3) and reported a less frequent intake of alcohol (0.4, 0.2-0.8). When results were adjusted for possible confounding factors in multivariate analyses, risk estimates were almost unchanged. These findings indicate that negative life events and hereditary factors may be risk factors for Graves' disease.