The effects of chronic treatment with ginseng saponin, saikosaponin, glycyrrhizin and flavin adenine dinucleotide (FAD) on the adrenal and thymus weight, and the size of the adrenal cortex and medulla were determined in intact or hypophysectomized rats. A high dose of ginseng saponin significantly decreased the thymus weight, although ginseng saponin and a low dose of adrenocorticotropin (ACTH) induced insignificant hypertrophy of the adrenals. Ginseng saponin evoked a significant increase in the relative thickness of the adrenal cortex. Saikosaponin d increased the area of the adrenal cortex, but not that of the medulla, and induced adrenal hypertrophy and thymus atrophy, whereas saikosaponin c did not affect the weight of either. A high dose of glycyrrhetinic acid, like ginseng saponin, induced thymus atrophy, but not adrenal hypertrophy. FAD evoked adrenal hypertrophy in dexamethasone-treated rats but not in control rats. In hypophysectomized rats these effects of ginseng saponin, saikosaponin d and FAD disappeared, while a low dose of dexamethasone or ACTH induced thymus atrophy or adrenal hypertrophy, respectively.