To investigate the status of the Na+ concentrations [Na+]i, K+ concentrations [K+]i and ionic fluxes in red cells of human subjects with abnormal thyroid function, we measured the Na(+)-K+ pump activity as well as Na(+)-K+ cotransport (CoT), Na(+)-Li+ countertransport (CTT) and Na+ passive permeability in erythrocytes of 37 normal subjects, 19 untreated hyperthyroid patients, 12 treated hyperthyroid patients and 9 hypothyroid patients with T4 replacement. The mean [Na+]i value in the untreated hyperthyroidism group was significantly higher than that in the normal subjects (p less than .05), but not significantly different from that in the treated hyperthyroidism group. The mean [Na+]i value in the hypothyroidism with T4 replacement group, however, was significantly lower than that in the normal group (p less than .01). We did not find any significant difference of [K+]i in comparing each group. It was found that the Na(+)-K+ pump activity in erythrocytes was significantly increased in untreated hyperthyroidism (mean; 23.4% above control, p less than 10(-5], but there was no significant difference in treated hyperthyroidism and hypothyroid patients with T4 replacement. The rate constant for ouabain-sensitive Na+ efflux in the hypothyroidism with T4 replacement group was markedly higher than that in normal subjects (p less than .01), but not significantly different in the untreated hyperthyroidism group. We observed a significant increase of the Na+ CoT value in the patients with untreated hyperthyroidism as compared with that of the normal subjects (p less than .05), but there was no significant difference in the patients treated for hyperthyroidism and the hypothyroidism with T4 replacement group. However, the rate constant for Na(+)-CoT in the patients with hypothyroidism with T4 replacement was significantly higher than that in normal subjects (p less than .05). We observed a marked decrease of Na(+)-Li+CTT value in the patients with untreated hyperthyroidism versus that in the normal group (p less than .01). Passive Na+ permeability in the patients with untreated hyperthyroidism was markedly increased (p less than .05), and was markedly decreased in the patients with hypothyroidism with T4 replacement compared to normal subjects (p less than .01). It can be concluded from these studies that an increase in Na(+)-K+ pump activity in the patients untreated for hyperthyroidism might then be regarded as a secondary adaptive cellular response to higher [Na+]i values due to enhanced passive Na+ permeability, rather than a direct effect of the thyroid hormone.