Steady-state nortriptyline plasma levels were determined in eight patients at 9 AM, 12 PM, 3 PM, and 6 PM during treatment with nortriptyline hydrochloride administered as a single daily bedtime (hs) dose at 10 PM and repeated after changing the dosage schedule to three times a day (tid) with divided doses at 10 AM, 4 PM, and 10 PM. Overall, the mean levels were stable during the sampling period and comparable on the two schedules. As expected, the plasma level decreased at the later sampling times on the hs schedule and increased on the tid schedule. In seven of the eight patients, the differences on the two dosage schedules were less than 30 ng/ml, which is not considered clinically significant. One patient had a higher plasma nortriptyline level on the tid schedule, which was clinically significant. Standardization of sampling time is of importance when comparing plasma levels and therapeutic response in treatment studies.