In the newborn several situations of hyperinsulinism can be associated with myocardial hypertrophy and increased contractility. Insulin and the insulin-like growth factors (IGF) are derived from a common ancestral molecule. Insulin exerts mainly metabolic action, whereas the IGFs promote cell multiplication and differentiation. Using an assay system of cultured neonatal myocardial cells the stimulatory action of insulin and the insulin-like growth factors I and II on myocardial cell contractility was investigated. Spontaneously beating aggregates of myocardial cells were synchronized by an electric impulse generator. Contractility was measured via the amplitude of contraction by an optoelectronic system. Insulin at a concentration of 6,250 and 12,500 microU/ml increased the contractility by 11 and 18%; IGF-I at a concentration of 12 and 25 ng/ml, and IGF-II at a concentration of 25 and 50 ng/ml increased the contractility by 16 and 22%, and 13 and 18%, respectively. Lower concentrations did not provoke a significant increase in contractility. Insulin only in supraphysiological doses increases the contractility of neonatal myocardial rat cells, whereas both insulin-like growth factors act in physiological concentrations. Therefore, during hyperinsulinism insulin may increase myocardial contractility via the IGF receptor and not via the insulin receptor.