Primary cultures of myocardial cells from neonatal rats were exposed for up to 5 days to the cyclic AMP derivative 8-Br-cAMP. After one day of exposure to the nucleotide, an increase in specific binding capacity of the hydrophilic beta-adrenoceptor antagonist 3H-CGP 12177 was observed in intact cells. (-)-Isoprenaline displaced the radioligand from its binding site. Neither the KD of the antagonist, nor that of the agonist were significantly affected by 8-Br-cAMP. The loss of beta-adrenoceptors during desensitization by long term treatment of the cells with isoprenaline could be partially prevented by 8-Br-cAMP. Only in desensitized, but not in normal cells was isoprenaline-induced cAMP formation significantly enhanced by 8-Br-cAMP pretreatment. This may indicate that beta-adrenoceptors which appear during 8-Br-cAMP exposure are poorly coupled to the adenylate cyclase. Alternatively, the change in receptor density may be accompanied by alterations of other components in the beta-adrenergic system, e.g. an inhibition of the adenylate cyclase. We suggest that cAMP-dependent feed-back regulation of the beta-adrenergic system may play a role during postnatal myocardial differentiation.