Intermittent loss of the delta wave in the Wolff-Parkinson-White (WPW) syndrome may result from precarious conduction over the accessory pathway and, as such, would predict a benign prognosis in the event of the occurrence of atrial fibrillation (AF). We evaluated 52 consecutive patients referred for the assessment of the WPW syndrome and determined the prevalence of intermittent preexcitation using review of serial electrocardiograms, ambulatory monitoring, and treadmill testing. All patients subsequently had electrophysiologic testing using standard techniques to determine the properties of the accessory pathway. Of the 52 patients, 26 (50%) were found to have intermittent preexcitation as defined by loss of the delta wave with concomitant prolongation of the P-R interval on at least 1 occasion. These patients had longer effective refractory periods of the accessory pathway (356 +/- 114 versus 295 +/- 29 ms, mean +/- standard deviation, p less than 0.05) and longer shortest cycle lengths maintaining 1:1 anterograde conduction (426 +/- 171 versus 291 +/- 63 ms, p less than 0.02) than their counterparts with constant preexcitation. During AF, 15% of patients with intermittent preexcitation had shortest R-R intervals between preexcited beats less than 250 ms, versus 50% of patients with constant preexcitation (p less than 0.01). These data support the hypothesis that intermittent preexcitation suggests a benign prognosis in the event of AF. A careful search for intermittent preexcitation may yield important prognostic information in asymptomatic subjects and obviate further investigation.