Very-low-density lipoprotein (VLDL) and chylomicrons (CM) transport triacylglycerol (TAG) to peripheral tissues. Lipoprotein-TAG may gain access to target cells by lipoprotein lipase (LPL) hydrolysis or via receptor-mediated uptake; the principal routes of entry of VLDL and CM into heart is unknown, and different routes of entry may result in different metabolic fates. To examine this, isolated working rat hearts were perfused with rat VLDL and CM, dual labelled with [3H]TAG and [14C]cholesterol. Uptake and utilisation of CM-TAG were significantly greater than VLDL-TAG, but both were decreased significantly (more than halved) by tetrahydrolipstatin (THL, an inhibitor of lipoprotein lipase). By contrast, uptake of VLDL-cholesterol was much higher than CM-cholesterol (p<0.01), and suramin (a lipoprotein receptor antagonist) decreased cholesterol uptake of both forms. CM-TAG oxidation rate was more than 4-fold higher than VLDL-TAG oxidation. However, suramin decreased TAG oxidation from both VLDL and CM without affecting TAG uptake or total utilisation, suggesting that the TAG gaining access through receptor-mediated pathways is preferentially "channelled" towards oxidation. Most (79%) CM-TAG was oxidised whilst the proportion of VLDL-TAG oxidised was only about half (49%). In the presence of suramin, there was a significant increase in esterification (incorporation of assimilated [3H]TAG into myocardial tissue [3H]lipids, mainly TAG) of assimilated TAG from both VLDL and CM, again suggesting that receptor-mediated TAG uptake is directed towards oxidation rather than esterification. The importance of this relatively small pool of TAG is indicated by the fact that cardiac mechanical function declined markedly when lipoprotein receptors were inhibited. These results suggest that CM, most fatty acids of which gain access into cardiomyocytes through LPL-mediated hydrolysis, are the major supplier of TAG for hearts to oxidise; however, the metabolic fate of VLDL was split evenly between oxidation and deposition as myocardial tissue lipid. Most importantly, VLDL may play a regulatory role in heart lipid metabolism through a lipoprotein receptor-mediated mechanism.