Nephrectomy of mature rats was found to result in a significant increase in the circulatory half-life of tritiated ovine lutropin. The interaction of the glycoprotein hormone with the kidneys was studied in a more direct fashion using electron microscopic autoradiography. Evidence is presented showing the transfer of the hormone from microvilli into tubular epithelia (probably via vesicular transport), where radioactivity then becomes associated with lysosomes. This provides direct support for related results based on subcellular fractionation in which renal lysosomal catabolism was suggested as being important in the degradation of tritiated lutropin (M. Ascoli, R. A. Liddle, and D. Puett, Molecular and Cellular Endocrinology 4, 297, 1976). These results add substantial weight to the growing evidence that the kidneys assume a major role in controlling the concentration of circulating macromolecules.