In several genetic hypertensive rat strains, transplantation studies have established that the kidney carries at least a portion of the genetic message for hypertension. In man it has, of course, been more difficult to obtain clearcut results. This historical prospective observational study, double-blinded for knowledge of donors' and recipients' family history for hypertension, concerns 85 transplanted patients, not treated with cyclosporine and with stable renal function, followed up for an average of 8 yr. Both the donors' and the recipients' families were carefully characterized for presence or absence of hypertension. After transplantation, in recipients without hypertension in their own families, a kidney coming from a "hypertensive" family determines less withdrawal and more introduction of antihypertensive therapy (AHT) than a kidney from a "normotensive" family (odds ratio for AHT introduction 5.0, confidence interval, 1.4 to 17.8; P = 0.017). In recipients with familial hypertension, the origin of the kidney does not influence the prevalence of hypertension after transplantation. More detailed analyses show that, in recipients without familial hypertension, the transplantation of a "hypertensive" kidney determines a tenfold larger increase in the requirement of antihypertensive therapy than the transplantation of a "normotensive" kidney, to obtain a similar blood pressure control (P = 0.003). This results is confirmed by the analysis of time-profile trends for antihypertensive therapy, adjusted for missing data, in the most clinically stable period (2nd to 10th yr after transplantation). The transmission of familial hypertension with the kidney is thus seen only in recipients coming from "normotensive" families, because a familial tendency for hypertension blunts the effect of receiving a "hypertensive" kidney.