The metabolism of long chain fatty acids was investigated in the failing heart of guinea pigs with chronic constriction of the ascending aorta. Homogenates prepared form failing hearts exhibited (a) a decreased capacity to oxidize palmitic acid (failure = 0.50 +/- 0.06 mumole/g of protein per 20 min; control = 1.09 +/- 0.10); (b) a reduced level of carnitine, a myocardial constituent which serves to control the oxidation rate of long chain fatty acids in the heart (failure = 0.91 +/- 0.10 mumole/g wet weight; control = 1.69 +/- 0.10); and (c) an increased rate of palmitate incorporation into triglycerides and lecithin. Exogenous carnitine effected a restoration of the defective palmitate metabolism of the homogenates towards normal. In contrast to long chain fatty acid oxidation, glucose oxidation by the failing heart was not impaired. As a consequence of this selective lesion in energy substrate utilization, the failing heart might be forced to rely on substrates other than long chain fatty acids for its major energy supply.