This study examines stress, coping, and regimen adherence as determinants of chronic and transient metabolic control in diabetes. We also examine the interaction of biologic vulnerability and psychosocial risk factors to see if Type 1 (insulin dependent diabetes mellitus) or Type 2 (noninsulin dependent diabetes mellitus) diabetes had greater responsiveness to psychosocial risk factors. Analyses of data from insulin-treated adults with Type 1 (N = 57) and Type 2 (N = 61) diabetes supported the biopsychosocial model. For Type 1 diabetes, self-controlling persons had better glycemic control and emotional persons had worse (because of differences in stress). All of these associations were mediated by regimen compliance. For Type 2 diabetes, self-controlling persons had better glycemic control for reasons other than regimen compliance. There was an interaction between biologic and psychosocial factors, with psychosocial factors accounting for more variance in glycemic control within Type 1 patients. Stable psychosocial resources (i.e., education, being married, and positive coping styles) were associated with better chronic glycemic control, while stress and regimen nonadherence were associated with worse transient glycemic control.