The elimination of imipramine (IMP) from the brain regions was investigated in rats after a single 5 mg/kg or 20 mg/kg intraperitoneal administration. At both 5 mg/kg and 20 mg/kg IMP injection, the brain regions could be divided into two classes in terms of IMP elimination. IMP levels in plasma and class A brain regions (cerebellum, mid-brain and medulla, striatum, posterior cortex and frontal cortex) declined according to a monoexponential profile with the same elimination rate constant and the time courses only shifted in parallel depending on the dose. On the other hand, the disappearance of IMP in class B brain regions (hypothalamus, thalamus, hippocampus and nucleus accumbens) followed a biexponential profile. The initial phase was similar to that in the class A brain region at each dose. However, the later phase of the curves was identical regardless of the dose. It is suggested tha the class B brain region may possess the high-affinity and low-capacity binding site for IMP.