Biventricular pacing has recently been found beneficial in the treatment of congestive heart failure (CHF). Meanwhile, positron emission tomography (PET) has emerged as a new method to analyze glucose metabolism in the heart. Five patients (mean age 68.8 +/- 8.1 years, 4 men) who received biventricular pacing therapy for 5.8 +/- 6.6 weeks for CHF were studied. Myocardial glucose metabolism was evaluated by PET with fluoro-18-deoxyglucose (18F-FDG), and percent uptake (%uptake) of 18F-FDG was calculated during biventricular pacing and compared with that during 1 hour of conventional RV pacing. Biventricular pacing was associated with a significant decrease in NYHA functional Class from 3.67 +/- 0.52 to 2.50 +/- 0.55. After 18F-FDG PET, three of five patients remained clinically stable, and two died during follow-up. Mean 18F-FDG %uptake during biventricular pacing was not different than during short-term RV pacing (62.1 +/- 18.4 vs. 63.6 +/- 17.0%). However, patients who remained clinically stable had a lower value of 18F-FDG %uptake in the septal region than patients who died (46.9 +/- 5.6 vs 80.3 +/- 1.3%, P < 0.01). One patient whose cardiac function improved significantly also had a small septal region of decreased 18F-FDG uptake during RV pacing. In conclusion, biventricular pacing therapy was effective in this small group of patients with severe, drug-resistant CHF. An evaluation of the effects of biventricular pacing on glucose metabolism in the subacute phase may help identify patients with a favorable long-term response to this therapy.