SUMMARY Persons participating in a 5-day diagnostic protocol were routinely typed for ABO, Rh, MNS, Kell, Kidd, Duffy, P, Haptoglobln, phosphoglucomutase-1 (PGM-1), and add phosphatase (AcP). The study population was composed of 164 nonnotensive whites, 34 normotensive blacks, 161 whites and 43 blacks with essential hypertension, and 52 whites with secondary forms of hypertension (18 atherosclerotic reoovascular hypertensives, 17 patients with fibromuscular disease, and 17 patients with primary aldosteronism). There were no significant differences in phentotype frequencies in ABO, Rh, Kidd, Kell, Duffy, P, Haptoglobin, PGM-1 or AcP in any of the comparisons. However, there was a significantly different distribution of MNS phenotypes in comparisons of essential and atherosclerotic renovascular hypertensives with nonnotensive controls. Essential hypertensives had a lower frequency of the S gene and a higher frequency of s in whites (X3 = 12.21, p < 0.005). Atherosclerotic renovascular hypertensives differed from the normotensive population in the frequencies of both MN (X1 = 4.34, p < 0.05) and Ss (X1 = 4.21, p < 0.05). The finding of disease-blood group associations supports the hypothesis that there may be significant physiological differences between individuals of different blood types.