OBJECTIVE Recent studies assessing cardiovascular effects of desipramine (DMI) in pediatric patients consistently have found small, clinically benign, but statistically significant, increases in heart rate and electrocardiographic (ECG) conduction parameters. However, single, routine ECG recordings cannot fully assess potential infrequent rhythm disturbances. METHODS We analyzed data from 24-hour ECG monitoring, two-dimensional Doppler echocardiography, and expert clinical cardiac examination of DMI-treated patients. Subjects were 71 children (N = 35) and adolescents (N = 36) receiving long-term treatment (means +/- SD = 1.5 +/- 1.2 years, median = 1.0 year) with DMI (means +/- SD = 3.5 +/- 1.6 mg/kg). RESULTS Compared with previous observations in untreated healthy children. DMI-treated patients had significantly lower rates of sinus pauses and junctional rhythm, but significantly higher rates of single or paired premature atrial contractions and runs of supraventricular tachycardia. There was an association between DMI serum levels and paired premature atrial contractions, but no other associations were detected. CONCLUSIONS These findings support the impression from previous ECG studies that DMI-associated cardiac effects in pediatric patients are quite benign. Nevertheless, it remains to be ascertained whether even minor cardiac abnormalities may predict later, evidently rare, adverse cardiovascular effects that may include sudden death.