BACKGROUND: The psychosocial vulnerability model of hostility posits that hostile individuals, given their oppositional attitudes and behaviours, are more likely to have increased interpersonal conflicts, lower social support, more stressful life events (SL-E) and higher likelihood of depression. However, little research has tested this hypothesis using large-scale prospective samples. The present study aims to assess the predictive value of hostility for depressive mood.MethodData are from 3399 participants in the Whitehall II cohort study, aged 35-55 years at baseline (phase 1 1985-1988). Cynical hostility was measured at phase 1. Depressive mood was assessed at phase 7 (2002-2004). Sociodemographic characteristics, health-related behaviours, common mental disorders and antidepressant medication intake were assessed at phase 1. SL-E and confiding/emotional support were measured at phases 1, 2 (1989-1990) and 5 (1997-1999). RESULTS: Compared with participants in the lowest quartile of cynical hostility, those in the highest quartiles were more likely to have depressive mood [second quartile: odds ratio (OR) 1.58, 95% confidence interval (CI) 1.14-2.20; third quartile: OR 2.78, 95% CI 2.03-3.77; fourth quartile: OR 4.66, 95% CI 3.41-6.36] in analysis adjusted for sociodemographic characteristics. This graded association was somewhat attenuated (18%) but remained robust to adjustments for the covariates measured at baseline and follow-up. The association was also evident in participants free of mental health difficulties at baseline. CONCLUSIONS: Cynical hostility is a strong and robust predictor of depressive mood. Consideration of personality characteristics may be crucial to the understanding and management of depression.