Left ventricular myocardial blood flow and metabolic parameters were studied in dogs with severe heart failure induced by rapid ventricular pacing. The impact of early administration of enalapril was also evaluated. Seventeen dogs were randomly assigned in a blinded fashion to receive enalapril at a dose of 10 mg orally per day or a matching placebo commencing 1 week after initiation of pacing. Six dogs underwent sham operations and served as a control for the myocardial blood flow and metabolic studies. In general, there was no significant difference in myocardial blood flow among the control dogs, the placebo-treated, and the enalapril-treated, paced dogs. However, tissue adenosine triphosphate was markedly reduced in both the enalapril-treated, paced dogs (2.43 +/- 0.55 mumol/gm wet weight, mean +/- SD) and the placebo-treated, paced dogs (2.79 +/- 0.39 mumol/gm) compared with the level in control dogs (4.77 +/- 0.88 mumol/gm, both p < 0.01). Tissue glycogen and lactate levels were similar in the three groups. The time to development of severe heart failure tended to be longer in the enalapril-treated dogs (33 +/- 12 days) than in the placebo-treated dogs (24 +/- 10 days, p = 0.07). In pacing-induced heart failure, therefore, an imbalance between energy supply and demand may contribute to the left ventricular dysfunction, myocardial ischemia does not play a major role, and early treatment with enalapril may prolong the time to development of severe heart failure.