The impact that substance use has on an individual with mental illness has been documented; however, little is known about the impact that this may have for a family caregiver. Data was collected in a cross sectional study using mailed questionnaires to a convenience sample of family members of persons with mental illness (n = 110). Hierarchical linear regression analysis was used to determine the impact of substance use status upon four measures of well-being within a stress-coping model. The variables within the model were able to account for a significant proportion of the variance in each of the measures: perceptions of burden, depression, anxiety and physical health status (R[superscript 2] = 0.419 to 0.202). However, substance use status was not a significant predictor in any of these equations. Symptomatology and a measure of specific social support were the most significant predictors of burden ([beta] = 0.345, p less than 0.001 and [beta] = 0.330, p less than 0.001). Perceptions of caregiver burden were found to be the most significant predictor in each of the other three analyses ([beta] = 0.515, p less than 0.000; [beta] = 0.511, p less than 0.000; [beta] = -0.571, p less than 0.000). Results of this study suggest that substance use may not be as important as the other predictors included in the model in determining the well-being of family caregivers. (Contains 2 tables.)