The fibrinolytic and metabolic changes associated with doxazosin treatment were evaluated in 20 patients with mild to moderate hypertension. Steady-state plasma glucose (SSPG) concentration was used to subdivide hypertensive patients into two groups of 10 each: Insulin-resistant (SSPG > 190 mg/dl) and nonresistant (SSPG < 190 mg/dl). The blood pressure was normalized after 4 to 6 months of doxazosin treatment in both groups, but it was associated with significantly lower fasting plasma triglyceride level, lower integrated insulin response to a 75 gm oral glucose load, lower SSPG concentration, significant decreases in plasma plasminogen activator inhibitor type one antigen and activity and tissue plasminogen activator antigen, and a significant increase in tissue plasminogen activator activity only in the insulin-resistant group but not in the nonresistant group. It was also noted that the improvement of the fibrinolytic and metabolic abnormalities in the insulin-resistant group tended to return to the less abnormal levels seen in the non-resistant group. The data suggested that doxazosin treatment of hypertension attenuated much of the abnormalities of insulin resistance but had little effect on insulin-sensitive patients. It may support a link between impaired fibrinolysis and insulin resistance in patients with hypertension.