Because an inherited renal factor may contribute to essential hypertension in humans, the study of family members is attractive. To assess the determinants of renal vascular tone, graded doses of either diltiazem (10-1000 micrograms/min) or acetylcholine (1-100 micrograms/min) were infused into the renal artery in 52 normotensive subjects, 16 with and 36 without a family history of hypertension when they were in balance on either a 10-mEq or 200-mEq sodium intake. Renal blood flow was measured with 133Xe. Restricted sodium intake potentiated renal vascular responses to diltiazem (p less than 0.01), suggesting a role for angiotensin as a determinant. In four subjects with no family history of hypertension on a 200-mEq sodium intake, angiotensin II in subpressor doses (1 ng/kg/min i.v.) induced renal vasoconstriction and enhanced the renal vasodilator action of diltiazem (p less than 0.001). In subjects with a family history of hypertension, the renal vascular response to diltiazem was enhanced (p less than 0.01) despite similar values of plasma renin activity, angiotensin II concentration, and sodium excretion. Because responses to acetylcholine were modified neither by sodium intake nor by family history, specificity for diltiazem was suggested. The intriguing possibility is raised that the enhanced renal vascular response to diltiazem reflects an abnormality in the control of renal vascular tone in the offspring of essential hypertensive subjects.