Quinidine syncope and factors associated with it are well known among adult patients treated for cardiac arrhythmias. To define factors that may influence the occurrence of syncope in children taking quinidine, the clinical, anatomic, electrocardiographic, roentgenographic and pharmacologic data were compared in six patients with syncope (Group A) and 22 patients without syncope (Group B). There was a significant (chi-square = 10.2, p = 0.001) relation between heart disease and quinidine syncope: all six Group A (syncopal) patients had heart disease whereas 15 of the 22 Group B (non-syncopal) patients had no structural heart disease. In contrast, no significant difference was noted between Group A and Group B patients in mean age (11.4 versus 11.4 years), mean quinidine serum concentration (2.9 versus 2.3 micrograms/ml), mean corrected QT interval before quinidine (0.43 versus 0.40 second) or mean corrected QT interval during quinidine therapy (0.46 versus 0.46 second) or between those taking digitalis and those not. Two of the six Group A (syncopal) patients died during therapy, one 6 days after initiating therapy and one suddenly at home 6 months after beginning quinidine. Another two of the six Group A patients exhibited hypokalemia (both 2.9 mEq/liter) at the time of syncope, 2 weeks and 6 months, respectively, after initiation of quinidine therapy; both survived. Syncope occurred within 8 days of initiation of quinidine therapy in three of the six patients. Sustained ventricular tachycardia was observed during quinidine associated arrhythmia in three of six patients with syncope; nonsustained ventricular tachycardia or complex ventricular ectopic activity while on this therapy was observed before syncope in the other three patients in Group A.(ABSTRACT TRUNCATED AT 250 WORDS)