Extremely small quantities of corticotropin tend to give positive values in the ascorbic acid depletion test in hypophysectomized rats. This effect was observed with doses from 1/25,000 to 1/400,000 I. U. per 100 g. body wt. The differences from the expected zero values were highly significant. The total no. of hypophysectomized rats used for the present investigation was 493; 153 served as saline-treated controls; the others were treated with U.S.P. Corticotropin Reference Standard and with a commercial corticotropin prepn. It is suggested that the phenomenon is due to the fact that corticotropin exerts a double effect on the adrenals, i.e., a diminution to the total content of ascorbic acid and a diminution of the adrenal wt., and that these 2 effects do not run parallel.