The functional role of β 3-adrenergic receptors in the heart is still not clear. The actions of two widely used β 3-adrenoceptor agonists, such as BRL 37344 and CGP 12177, were studied in the isolated guinea pig heart, perfused at constant pressure according to the Langendorff technique. Heart contractility (dP/dt, first derivative of pressure measured over time) and coronary flow (CF) were assessed simultaneously. BRL 37344 and CGP 12177A at a concentration range of 10− 8–10− 5 M increased dP/dt and CF. The selective β 3-antagonist L-748337 (10− 6 M) did not significantly influence either BRL 37344 or CGP 12177A–induced responses. However, both dP/dt and CF responses to BRL 37344 and CGP 12177A at a concentration of 10− 7 M were abolished in the presence of the β 1/β 2-antagonist nadolol (10− 5 M). In contrast, cardiovascular responses to CGP 12177A at a higher concentration of 10− 5 M were hardly inhibited by nadolol (10− 5 M). In addition, BRL 37344 and CGP 12177A at concentrations as low as 10− 8 M almost completely abolished an isoprenaline-induced increase in contractility, suggesting that both BRL 37344 and CGP 12177A display β 1-antagonistic properties. These data suggest that the stimulatory cardiovascular responses to BRL 37344 at a full range of concentrations, and CGP 12177A at a low concentration of 10− 7 M, are not mediated by β 3-adrenergic receptors, but rather by activation of β 1-or β 2-adrenergic receptors. Cardiovascular effects of CGP 12177A at a high concentration of 10− 5 M are independent of β 1/β 2/β 3-adrenergic receptors. Summing up, it seems that in the isolated guinea pig heart the functional role of β 3-adrenoceptors is not significant. Nonetheless, BRL 37344 and CGP 12177A are not ideal tools for investigation of β 3-adrenergic receptor-dependent effects, because these compounds interact with other types of β-adrenergic receptors.