Specifically guanidinated insulin, prolactin and placental lactogen are more active biologically than the corresponding native hormones on mouse mammary epithelium in vitro. The modified insulin is also more active than the native hormone on fat tissue and diaphragm from insulin-resistant obese mice. L-thyroxine and L-triiodothyronine enhance differentiative function induced by insulin, glucocorticoid and prolactin in mammary explants. They do not enhance non-differentiative functions. It appears that this action of the thyroid hormones is associated with that of prolactin.