The density of binding sites (Bmax) for 3H-imipramine was elevated in cerebral cortical, hypothalamic and hippocampal membranes from 24 month old male C57BL/6J mice. Cerebellar binding was constant with increasing age. There were no changes in the equilibrium dissociation constant (Kd) for 3H-imipramine in any brain region. The increase in the binding of 3H-imipramine induced by sodium and chloride ions in vitro was diminished in cerebral cortical homogenates from aged mice; both the sodium-sensitive and chloride-sensitive components of binding were about 50% less in aged mice. Dose-response curves indicated that the effectiveness with which chloride enhanced binding was similar with age, even though the absolute increase in binding was less. The rate of dissociation of 3H-imipramine from cerebral cortical homogenates was similar with age and serotonin slowed the rate of dissociation equally at all ages. Possible mechanisms for the age-related increase in brain 3H-imipramine binding are discussed. Ion-sensitive binding is discussed in relationship to the current controversy surrounding desipramine-sensitive versus ion-sensitive binding.