It has been shown that subjecting rats to an unpredictable stress regimen resulted in an enhanced myocardial sensitivity to catecholamines, but only if the plasma glucocorticoid levels were extremely high. It was inferred that the elevated levels of glucocorticoids were responsible for the changes in myocardial sensitivity. However, ACTH and related peptides have been shown to affect both the electrical and contractile response of skeletal muscle, independent of adrenal cortical secretions. In this study, the effect of the glucocorticoids, cortisol and corticosterone, and of synthetic ACTH and polypeptides related to ACTH on the myocardial sensitivity to catecholamines were investigated using the electrically driven atrial strip preparation of the rat. Both cortical hormones and ACTH were found to potentiate the inotropic response to noradrenaline, the potentiation being dose dependent, α-MSH (ACTH 1–13) did not potentiate the myocardial response to noradrenaline but rather at high doses inhibited the response. All other polypeptides testes, ACTH 4–10 D- and L-isomers, ACTH 1–16 ACTH 5–16 and ACTH 11–24 produced no significant change in myocardial sensitivity. As a consequence it would appear possible that the enhanced myocardial sensitivity to catecholamines seen following stress situations may result from both the glucocorticoids and the pituitary peptide, ACTH. It would also appear that as with the steroindogenic activity of the molecule, all of the first 24 amino acids of the ACTH peptide chain are required for its action on the myocardium.