Na-K-Cl cotransport was measured in 209 essential hypertensive patients (EH) and in 114 normotensive controls (NT). The distribution of Na-K-Cl cotransport was bimodal in EH and unimodal in NT. The EH with higher Na-K-Cl cotransport values had increased passive permeability to Na in fresh erythrocytes and increased Li-Na countertransport compared to NT. Li-Na countertransport was significantly increased in the EH as a whole, but the increase was accounted for by some EH individuals with elevated Na-K-Cl cotransport values. A simple biometric analysis of the Na-K-Cl cotransport was performed for 287 individuals of 86 families with different prevalence of hypertension (neither parent hypertensive, 39 families; one, 31 families; or both, 16 families). Na-K-Cl cotransport was not correlated between spouses, but was correlated highly significantly between the average value of the two parents (mid-parent) and offspring. The polygenic additive heritability (h2) was about 50% for all families considered together. It increased slightly for the hypertensive families analyzed alone (no significant correlation was found, and hence genetic heritability, in the normotensive families). Finally, after applying arbitrary cut-off points to the Na-K-Cl cotransport values, segregation analysis showed that some major gene, recessive for the high allele, also contributes to the phenotypic value of Na-K-Cl cotransport.