We examined the association between psychosocial stress-related variables and insulin resistance syndrome (IRS) risk-factor clustering. In 90 middle aged male volunteers, psychosocial stress-related variables, defined as feelings of excessive tiredness and as personality and behavioral factors reflecting a stress-inducing life style (type A behavior, hostility, and anger), were significantly correlated with the hyperinsulinemia, hyperglycemia, dyslipidemia, hypertension, increased abdominal obesity, and increased plasminogen activator inhibitor-1 (PAI-1) antigen comprising the IRS. The correlations remained significant after adjusting for body mass index (BMI), age, educational level, smoking status, alcohol consumption, and physical activity. However, the different Stress-related factors reflected different risk-factor clustering profiles. Type A behavior was associated with normotension and a normal metabolic profile (canonical r = .50, chi(2)(36) = 59.1, P = .008). Hostility was related to elevated systolic blood pressure (SBP) and elevated triglycerides (TGs) (canonical r = .38) chi(2)(14) = 23.2, P = .052, whereas feelings of excessive tiredness were related to abdominal obesity, augmented glycemic responses to glucose ingestion, dyslipidemia, and increased PAI-1 antigen (canonical r = .39, chi(2)(24) = 36.8, P = .046). Although hostility and feelings of excessive tiredness have partly overlapping but clearly different clinical and metabolic correlates, their combination represents a full-blown IRS. Thus, even though insulin resistance is presumably to some extent genetically determined, these results suggest that considering psychosocial stress may be beneficial in understanding IRS risk-factor clustering. Copyright (C) 1996 by W.B. Saunders Company