The relations of red blood cell sodium (RBC Na) and potassium (RBC K) concentrations to blood pressure and prevalence of hypertension were assessed for 1805 men and women, aged 25 to 74 years, who participated in the baseline examination of the Gubbio Population Study in north central Italy. In men, in univariate analyses, RBC Na concentration was not significantly related to systolic or diastolic blood pressure, while RBC K concentration was significantly and inversely related to blood pressure. In women RBC Na values correlated significantly and directly with systolic and diastolic pressure, but RBC K concentration was not significantly related to blood pressure. Results of the multivariate analyses indicated in men a significant independent and inverse relationship of RBC K concentration with hypertension and blood pressure, and in women a significant positive association of RBC Na concentration with hypertension. RBC Na did not relate independently to either systolic or diastolic blood pressure in men or women. Age-specific analyses suggested that the relationships between RBC K level and blood pressure in men and the relationship between RBC Na level and hypertension in women were stronger in older (age 55 to 74 years) compared to younger participants (25 to 54 years). These findings indicate that the associations of RBC Na and K concentrations and hypertension may be sex and age specific. The nature of these gender- and age-specific associations remains to be clarified. Prospective data are also needed for further clarification of the relation of intracellular Na metabolism to the etiology of hypertension.