BACKGROUND Endothelium-derived nitric oxide is an important mediator of exercise-induced changes in skeletal muscle blood flow. Given the recently documented effects of estrogens on nitric oxide synthase, it is hypothesized that oral contraceptives (OC) containing estrogen would increase nitric oxide production at rest and after endurance exercise. Further, we postulated that OC use would augment skeletal muscle blood flow at rest and during exercise. METHODS Fourteen women (non-smokers) were divided into two groups: control (CON; sedentary, normal menstrual-cycling women who have not used oral contraceptives for > or = 12 mons; 18-38 yrs old; n = 7), and oral contraceptive users (OC; sedentary women who have been using low-dose estrogen/progestin oral contraceptives for > or = 12 mons; 19-38 yrs old; n = 7). Measurements of forearm blood flow were obtained from each group, using strain gauge plethysmography, at rest and during an exercise protocol in which intermittent handgrip exercise was performed at 15%, 30%, and 45% of maximum voluntary contraction (MVC). Additionally, venous blood samples were taken before and after a 90 min treadmill walk for measurement of serum nitrate/nitrite, an indirect assessment of steady-state nitric oxide production. RESULTS There was no difference in forearm blood flow (ml/min/ 100 cc tissue) at rest (CON = 2.7; OC = 2.8); however, the hyperemic response to handgrip exercise was significantly (p < 0.05) lower in the OC group at 30% (9.0 vs CON = 14.2) and 45% (12.0 vs CON=17.0) of MVC. Serum nitrate values at rest and following 90 min of treadmill walking did not differ between groups (p > 0.05). CONCLUSIONS Contrary to our hypotheses, these data indicate a compromised hyperemic response in the forearm of OC users. Further, chronic OC use may not affect nitric oxide production during low intensity treadmill exercise.