We tested the hypothesis that sympathetic nerve responses to stimulation of chemoreceptors by hypoxia are exaggerated in borderline hypertensive humans. We compared responses to isocapnic hypoxia in eight borderline hypertensive subjects and eight normotensive control subjects matched for age, sex, weight, and height without a family history of hypertension. Measurements of heart rate, mean blood pressure, minute ventilation, and sympathetic nerve activity to muscle were made before and during hypoxia. We also measured responses to a period of voluntary apnea during hypoxia. There were no significant differences between the increases in heart rate, blood pressure, and ventilation in response to hypoxia in the two groups. However, during hypoxia sympathetic activity in the hypertensive subjects increased by 40.6 +/- 13.6% (mean +/- SE), greater than the increase of 20.4 +/- 5.0% in the control subjects (p less than 0.05). In six hypertensive and six control subjects, when apnea was performed during hypoxia, sympathetic activity increased by 605.0 +/- 294.3% in the hypertensive subjects and by only 52.8 +/- 17.3% in the control subjects (p less than 0.001). We conclude that the chemoreceptor reflex is enhanced in borderline hypertensive subjects and results in exaggerated increases in sympathetic nerve activity during hypoxia. This enhanced chemoreceptor reflex is especially obvious when the inhibitory influence of breathing and thoracic afferent activity is eliminated by apnea. This exaggerated response may contribute to excess sympathetic activity in borderline hypertensive subjects and to adverse consequences of sleep apnea in hypertensive subjects.