SUMMARY A polypeptide fraction isolated from the urine of nonnotenslve subjects lowers blood pressure (BP) in a rabbit bioassay (mean BP decrease 33.8% ± 0.6%, SEM). Patients with primary hypertension exhibit reduced or no activity (mean BP decrease 8.8% ± 1.2%). In contrast, patients with secondary forms of hypertension show activity like nonnotensives (mean BP decrease 33.4% ± 1.0%). Tbe results the bioassay in tbe two patient groups correlate well with the family inddence of hypertension (68% and 37% for primary and secondary hypertension respectively). Cases with borderline hypertension fall into two groups; a larger one with vasoactivity in the bioassay and lower family inddence of hypertension; and a smaller group reacting like patients with primary hypertension. Only the latter group may represent an initial stage of primary hypertension. In nonnotenslve children and young men, an inactive fraction was found in 31% and 28% respectively. These inactive groups had twice the family inddence of hypertension compared to the groups with vasoactivity. These results suggest the existence of a possible genetic marker of primary hypertension and may offer the possibility to detect disease before its manifestation.