Stress adversely affects glycemic control in patients with type II diabetes mellitus. In addition, stress reduction with relaxation techniques or medication use in the management of hyperglycemia has been recommended. This study examined the relationship of glycemic control to self-reported stress in 19 patients with type II diabetes mellitus who were randomly allocated to receive either glyburide or glipizide for 16 weeks in a double-blind crossover design. Each treatment phase was preceded by a 2-week washout period. A previously designed and validated nine-item stress questionnaire was used to assess areas such as safety, financial wellbeing, energy level, health, etc. These areas were evaluated as more/less, better/worse, or no change. The stress questionnaire, fasting blood glucose (FBG), and glycosylated hemoglobin (GHb) concentrations were completed or measured at the end of glyburide and glipizide treatment periods. By assigning a value of 1, 2, or 3 to a positive, no change, or negative response, respectively, a composite stress score was computed and compared with glycemic control as assessed by FBG and GHb. Regression analysis showed highly significant correlations (P < .05) between stress scores and FBG (r = .70) as well as GHb (r = 0.84) with glipizide therapy. No such correlation was noted with glyburide (FBG: r = 0.29; GHb: r = 0.29). These findings suggest that during glyburide treatment, in contrast to glipizide, an increase in stress was not associated with a corresponding rise in blood glucose or worsening of metabolic control.(ABSTRACT TRUNCATED AT 250 WORDS)