Imipramine was used to treat 18 depressed inpatients for 22 days. Imipramine 2 mg/kg/day was administered from day 0 to day 14 intramuscularly, and 4 mg/kg/day was administered orally from days 15-21. Two pharmacokinetic studies were performed, the first at the end of the intramuscular phase (day 14) and the second at the end of the oral phase (day 21). Imipramine and desipramine blood levels were measured every hour from 8 a.m. to 4 p.m. Between these two pharmacokinetic evaluations, blood levels of imipramine and desipramine were measured every morning at 8 a.m. During intramuscular administration, the parent drug imipramine predominated in the plasma and, conversely, the desmethylated metabolite predominated during oral administration. With the changeover in route of administration, the doubling of the dose kept the blood levels of imipramine equal, while desipramine increased; the sum of imipramine and desipramine also increased, and the ratio of imipramine and desipramine decreased sharply, the median ratio changing over 3 days from 1.50 (day 15) to 0.62 (day 18).