The effect of treatment with the factor that inhibits the release of melanocyte stimulating hormone (MSH) identified as 1-prolyl-1-leucylglycinamide (MIF) on brain catecholamine synthesis was examined in normal and hypophysectomized rats. The tripeptide induced a dose-related increase in striatal dopamine synthesis in slices obtained from treated normal animals but not in hypophysectomized animals. Hypothalamic norepinephrine synthesis was unaltered by MIF treatment in normal as well as in hypophysectomized rats. In addition, dopamine and norepinephrine syntheses were depressed in untreated hypophysectomized animals, as compared to normal controls. These results constitute the first direct demonstration of a central neurochemical effect of a hypothalamic factor.