In order further to understand factors affecting cholesterol metabolism in adult animals, we have studied the effect of a central nervous system stimulant, methylphenidate (Ritalin), on brain cholesterol metabolism. Structurally, this compound is related to compounds having a hypocholesterolemic effect (1,2,3), and also acts as a central nervous system stimulant(4). A preliminary report of these experiments has been published (5). The present paper is a more complete study of the effect of this drug on acetate incorporation into brain cholesterol.Experimental. Radioactive precursors. Acetate-2-3H (10 mC/m-mole); acetate-l-14C (2.8 mC/m-mole); acetate-2-14C (1.5 mC/m-mole) were used simultaneously in these studies. Radioactive nutrients were dissolved in physiological saline, with benzyl alcohol (0.9%) added as a preservative. The resultant solutions were injected intraperitoneally.The drug (methylphenidate) Ritalin, donated by Ciba Pharmaceutical Co. (H. Sheppard), was prepared as a 1% solution in saline....