Estrogens play a major role in mineral homeostasis, however it remains unclear whether they exert regulatory action upon reabsorption of phosphate (P(i)) in proximal tubules of the kidney. We investigated the effect of beta-estradiol E2 injected to thyroparathyroidectomized and ovariectomized rats upon Na+ cotransport of P(i) and other solutes across renal brush border membrane (BBM). In BBM from kidneys of E2-treated rats the capacity for Na+-P(i) cotransport was considerably suppressed (delta% - 42; P<0.01) whereas Na+-cotransports of L-proline D-glucose and SO4 across the same BBM did not differ from controls. We surmise that E2 inhibits selectively Na+-P(i) cotransport by direct interaction with E2 receptors in proximal tubular cells. These results indicate the existence of the inhibitory effect of estrogens upon renal proximal tubular Na+-P(i) cotransport and, by extention, proximal P(i) reabsorption. We suggest that this modulatory action of E2 plays a role in pathophysiology of mineral metabolism due to estrogen deficiency and should be considered when estrogens are used for pharmacotherapy of postmenopausal osteoporosis and some types of cancer.