It has been previously established that hypophysectomy leads to renal atrophy in rats and that a crude pituitaryderived fraction is effective in restoring kidney weight to the level expected for intact animals of the same body weight. This paper reports that considerable purification ofthe crude renotropic fraction from ovine pituitaries has been achieved and that the purified fraction is capable of restoring kidney weights of hypophysectomized castrated rats to normal values. For example, after five daily subcutaneous injections (135 jig/day) there were significant increases in dry kidney weight and total renal protein and DNA. The pituitary-derived fraction was devoid of somatotropin, contained only trace amounts of corticotropin, y-lipotropin, vasopressin, and prolactin, and had only low levels of thyrotropin and follitropin. Daily injections of prolactin, thyrotropin, and follitropin in doses of 20 jig each failed to stimulate renal growth in hypophysectomized rats. Thus, it seems highly unlikely that these factors are responsible for the observed renal hyperplasia after treatment with the pituitary fraction. The purified renotropic fraction had an isoelectric pH between 8 and 9. On polyacrylamide gel electrophoresis in the presence of detergent and a reducing agent, the renotropic fraction exhibited two major bands and one minor band with mobilities that corresponded to those of a standard lutropin preparation. The renotropic fraction exhibited considerable crossreactivity with an antiserum directed against the lutropin a subunit, suggesting the presence of the common glycoprotein hormone subunit. Moreover, the purified fraction stimulated steroid production by Leydig tumor cells in vitra It is noteworthy, however, that standard ovine lutropin at 135 jig/day failed to exhibit renotropic activity in hypophysectomized castrated rats, although effects were noted at twice that dose. It appears that the renotropic activity represents a pituitary substance that can be separated from lutropin only with difficulty.The pituitary is believed to be essential for maintaining normal kidney size because hypophysectomy leads to renal atrophy (1, 2) and prevents the compensatory renal hypertrophy that occurs after unilateral nephrectomy (1,3,4). An earlier study in this laboratory demonstrated that a pituitary-derived fraction restored the atrophic kidneys of hypophysectomized rats to the weights expected for normal animals of the same body weight (5). Treatment with somatotropin (GH) and corticotropin (ACTH) failed to mimic this effect. This renotropic activity was also observed in hypophysectomized castrated rats, demonstrating that the activity was not mediated solely by androgens which are known to stimulate renal growth in rats (6). In addition, human choriogonadotropin (hCG) was ineffective in restoring the renal weight of hypophysectomized castrated rats (5).In an effort toward final purification and characterization of the pituitary-derived renotropin, the crude renotropic fraction from ovine pituitaries h...