18-Hydroxytestosterone inhibited the renal electrolyte effects of DC A and aldosterone in acute experiments with adrenalectomized rats. Comparative tests show that it is approximately as potent as spironolactone parenterally and considerably more potent than testosterone; orally, it is ineffective, not unlike testosterone. Available evidence indicates that 18-hydroxytestosterone is pharmacodynamically a specific antagonist of mineralocorticoids which competes reversibly with mineralocorticoids for target tissues. Androgenic and myotrophic properties were adversely affected with the 18-hydroxy modification. (Endocrinology 74: 999, 1964) A PRACTICAL method for synthesis of x x 18-oxygenated steroids from the alkaloid conessine was described by Pappo (1). This procedure made available supplies of 18hydroxylated derivatives of deoxycorticosterone, its acetate and progesterone for biological tests in the past (2). Recently, experience in the laboratory was extended to another derivative in the series of 18-oxygenated steroids, 17/3,18-dihydroxy-4-androsten3-one or 18-hydroxytestosterone (18-OHT), for which no data appear to exist. Results of our study, described herein, indicate the 18-hydroxy analog of testosterone is a mineralocorticoid antagonist, without important androgenic or myotrophic properties. Materials and Methods Renal electrolyte properties of 18-OH-T were investigated in acute experiments with salineloaded adrenalectomized rats weighing 150-200 g. In general, the test procedures involved the treatment subcutaneously or orally with corn oil solutions of the compound, followed by collection of a 4-hr urinary specimen in metabolism cages (4 animals/cage). Antimineralocorticoid effects were assessed by reversal of the urinary electrolyte manifestations of a standard dose of deoxycorticosterone acetate (DCA) or d-aldosterone-21-acetate. Pooled s values in these studies are 0.092, 0.074 and 0.084 per 4animal response for log Na, K and (Na X10) /K, respectively (degrees of freedom =60). Other details of the test procedures have been described elsewhere (3). Androgenic and myotrophic activities of 18-OH-T, injected in oil intramuscularly for 7 days, were determined in castrated male rats by examination of weights of the seminal vesicle, ventral prostate and levator ani (4). Statistical analyses for significance were done by Student's t test, relative potencies were computed by Irwin's method (5), and Received December 20, 1963. 1 The chemistry of 18-OH-T has been described in U. S. Patents 3,017,410 and 3,080,360. urinary Na and K were determined on the Beckman flame photometer. Results and Discussion Table 1 summarizes urinary electrolyte data of 2 replicate experiments, designed according to preliminary studies, with 18OH-T given alone and in various dosage combinations with mineralocorticoids in adrenalectomized rats. DCA at a 12 jug dose produced Na retention, K loss and a reduction of the ratio of Na/K in the urine relative to untreated controls, as expected of a mineralocorticoid; these manifestations of DCA were readily reversed with 1.2 and 4.8 mg of 18-OH-T. Similar inhibitory effects were noted with the testosterone derivative against d-aldosterone-21-acetate given at a dose equivalent in mineralocorticoid potency to that of DCA. In the absence of mineralocorticoids, 18-OH-T induced Na loss at the 4.8 mg dose (p<.05), but otherwise failed to demonstrate electrolyte effects that would oppose mineralocorticoid action. Pharmacodynamically, these data suggest that 18-OHT inhibits the renal effects of mineralocorticoids by specific antagonism rather than by physiological antagonism (6), to show thereby a characteristic in common with spironolactone (3) and testosterone (7). Noteworthy, furthermore, is the fact that blocking properties of the 18-hydroxy derivative were progressively reversed with increasing doses of a mineralocorticoid (cf responses obtained with combinations of 4.8 mg of 18-OH-T and 12, 60 and 300 Mg of DCA), which data strongly support the view of competitive interaction with the steroids, presumably at the kidney level. 18-OH-T was also tested comparatively 2 3 (3-Oxo-7a acetylthio -17/3 hydroxy 4 androsten-17a-yl)propanoic acid lactone.