To evaluate a possible cardiac pathophysiology of the chronic fatigue syndrome, we compared the resting cardiac function and exercise performance of 41 patients to those of an age-matched and sex-matched normal control group. Persistent fatigue following an acute apparently viral illness was the major complaint of all patients; none had specific cardiac symptoms nor abnormal physical findings. Electrocardiographic spatial patterns were normal in the patients, and there were no differences in the body surface sum of positive T-wave integrals between the patients (240 microV.x 10(2) +/- 107 microV.s x10(2)) and control (244 microV.x 10(2) +/- 108 microV.s x 10(2) subjects. Twenty-four hour ambulatory ECGs revealed no differences in sinus rates and incidences of ventricular dysrhythmias in the two populations. Left ventricular dimensions and systolic fractional shortening values were also similar in both groups; moreover none of the patients had segmental wall motion abnormalities. On graded exercise testing, 20 of 32 normal subjects achieved target (85 percent of age-maximum) heart rates, compared to four of 31 patients (p less than 0.001). The duration of exercise averaged 12 +/- 4 minutes for the normal subjects and 9+/- 4 minutes for the patients (p less than 0.01). The temporal profile of exercise heart rates was dissimilar in the two groups, with patients' rates consistently and progressively less than those of normal subjects. Peak heart rate averaged 152 +/- 16 beats per minute for the normal group vs 124 +/- 19 beats per minute for the patients (p less than 0.0001); in age-related terms, respectively, 82 +/- 6 percent of the maximum heart rate vs 66 +/- 10 percent (p less than 0.0001). Thus, patients with chronic fatigue syndrome have normal resting cardiac function but a markedly abbreviated exercise capacity characterized by slow acceleration of heart rate and fatigue of exercising muscles long before peak heart rate is achieved.(ABSTRACT TRUNCATED AT 250 WORDS)