The effects of imipramine treatment and plasma drug levels were studied in 20 prepubertal children (16 males, 4 females; age range 7-12 years) hospitalized for major depressive disorder (DSM-III criteria). No change in symptomatology was seen after 2 weeks of individual/group/family psychotherapy, but 12 children experienced a remission within 6 weeks of beginning imipramine. Response to the drug was concentration-dependent; of the children who achieved total tricyclic (imipramine plus desipramine) plasma levels of 125-225 ng/ml, 92% responded, compared with 25% of those outside this range. Antidepressant response was correlated both with total tricyclic plasma levels and with plasma desipramine levels (r = 0.72 and 0.56, respectively), but not with plasma levels of imipramine alone.