To identify better those subgroups of pacemaker recipients who will benefit from dual chamber pacing, 19 patients with DDD pacemakers that were physiologically paced were entered into a blinded, randomized protocol comparing long-term VVI versus DDD pacing. Patients were evaluated in each of the pacing modes for exercise performance, cardiac chamber size, cardiac output, functional status and health perception. Eight patients (42%) insisted on early crossover, from VVI to DDD pacing, after only 1.8 +/- 1.4 weeks because of symptoms consistent with pacemaker syndrome. Overall, 12 patients preferred DDD pacing and no patient preferred VVI pacing (p = 0.001). Percent fractional shortening (30 +/- 8 vs 24 +/- 6%, p = 0.009) and cardiac output (6.3 +/- 2.6 vs 4.4 +/- 2.2 liters/min, p = 0.0001) where significantly greater in the DDD mode. Exercise duration was greater during DDD compared with VVI pacing (11.3 +/- 3.7 vs 10.1 +/- 3.7 minutes, p = 0.006). However, it was only in the crossover subgroup that DDD pacing resulted in significant improvement in exercise performance and health perception compared with VVI pacing. This subgroup of patients was characterized by an intrinsic sinus rate of less than 60 beats/min (4/8 vs 0/11, p = 0.006), ventriculoatrial (VA) conduction (4/8 vs 1/11, p = 0.048), greater increase in exercise peak systolic blood pressure from VVI to DDD mode (21 +/- 12 vs 4 +/- 13 mm Hg, p = 0.02) and greater improvement in exercise capacity from VVI to DDD pacing (2.2 +/- 1.2 vs 0.6 +/- 1.4 minutes, p = 0.03) compared with the other 11 patients.(ABSTRACT TRUNCATED AT 250 WORDS)