Four studies were conducted in normal young and middle-aged men and women selected as high and low on hostility, evaluating vagal tone measures and effects of isoproterenol infusion on EKG T-wave and ST response after pretreatment with saline, neostigmine, and atropine. Demonstration that hostility was associated with deficient vagal anatagonism of SNS effects on the heart, especially in middle-aged as compared to younger persons, suggested that diminished vagal tone was one pathway whereby high hostility contributed to increased CHD risk. Clinical studies were then conducted to determine whether weaker vagal tone predicted increased myocardial ischemia and/or poorer outcomes in coronary heart disease patients.