Experiments were performed on normal male and female subjects to compare blood flow responses following release of an arterial occlusion (reactive hyperemia). Additionally, the effects of oral contraceptive therapy on the reactive hyperemia reaction were studied in female subjects. Forearm blood flow was measured with a strain-gauge plethysmograph, heart rate with an electrocardiograph, and mean arterial pressure was measured by auscultation. Blood flow was determined before and after circulatory arrest of 1, 3, and 5 min. Blood serum levels of 17β-estradiol, progesterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured by radioimmunoassay. The mean resting forearm blood flow was similar in males and females (∼4 ml/100 ml/min). There were no significant changes in systemic mean arterial pressure or heart rate during the experiments. Following 1 min of arterial occlusion, the peak blood flow responses were similar in males and females. The peak blood flow responses following release of arterial occlusion were lower in males than in untreated females at occlusion intervals of 3 and 5 min. Females receiving oral contraceptives showed reduced peak blood flow responses after circulatory arrest of either 3 or 5 min as compared to untreated females. There were no significant differences in the recovery times of the hyperemic responses between males and females following any of the periods of occlusion. The peak blood flow responses following 3 min of arterial occlusion were significantly correlated with the blood serum levels of 17β-estradiol, LH and FSH, but not with the blood serum levels of progesterone. These results suggest that: (1) sex difference has a marked effect on the blood flow response following arterial occlusion, and (2) hormonal changes influence vascular responsiveness in the female.