Intraerythrocytic sodium level (RBC Na) was measured on 1,800 normotensive members of 64 Utah pedigrees ascertained through hypertensive or normotensive probands, sibs with early stroke death, or brothers with early coronary disease. Likelihood analysis provided evidence that RBC Na was determined by four alleles at a single locus. Each allele was recessive to all alleles associated with a lower mean level. The four resultant distributions occurred in the frequencies: 0.8%, 89.3%, 9.7%, and 0.2% with corresponding means (mmol/1 RBC) of 4.32, 6.67, 9.06, and 12.19, respectively. The major locus explained 29.0% of the variance in RBC Na; polygenic inheritance explained another 54.6%. A higher frequency of the genotypes for high RBC Na in pedigrees when the proband was hypertensive than normotensive provided evidence that this major locus increases susceptibility to hypertension.