In 22 prepubertal depressed children, the total plasma concentration of imipramine and its major metabolite, desipramine, varied by more than sevenfold. The plasma drug concentrations correlated with slowing of intracardiac conduction, elevation of diastolic blood pressure, and increase in heart rate. These drug-induced changes were uniformly observed when the total tricyclic level exceeded 225 ng/ml. However, subjective reporting of nuisance side effects was not related to plasma drug concentration. These findings suggest that children can be safely treated when their plasma levels are below 225 ng/ml. If higher plasma levels are attained, closer monitoring is warranted.