To determine whether neuroticism, cognitive ability, and their interaction predicted mortality and to test whether neuroticism or cognitive ability effects were mediated by socioeconomic status (SES), physical health, mental health, or health behaviors. Participants were 4200 men followed up for > 15 years. Participants took part in telephone interviews and medical and psychological evaluations. The neuroticism measure was based on the Minnesota Multiphasic Personality Inventory, which was administered during the psychological examination. Cognitive ability was measured via the Army General Technical Test given at induction and Wechsler Adult Intelligence Scale subtests administered during the psychological examination, approximately 17 years later. We used covariance structure modeling to analyze the data because it enabled us to conduct Cox proportional hazards analyses with latent variables and mediator variables. Even after adjusting for age, ethnicity, and marital status, high neuroticism and low cognitive ability were independent mortality risk factors. A significant interaction indicated that participants high in neuroticism and low in cognitive ability were particularly at risk. In a second series of models, we examined whether education, income, seven physical health measures, two mental health measures, drinking, and smoking were related to mortality. SES and physical health variables attenuated the effect of cognitive ability but not that of neuroticism. A third series of models revealed that cognitive ability was related to mortality via its direct effects on income and health. The effects of high neuroticism, low cognitive ability, and their interaction predict mortality. Cognitive ability effects are mediated by health, income, and education.