Alpha-1-acid glycoprotein concentration and imipramine binding to plasma proteins were determined in a cohort of 69 subjects, aged 20-97 years. No subject had evidence of acute or chronic inflammatory disease or malignancy, or was receiving tricyclic antidepressant therapy. Alpha-1-acid glycoprotein concentration increased significantly with increasing age (r = 0.28; P less than 0.02). Imipramine percentage not bound to plasma proteins was negatively related to alpha-1-acid glycoprotein concentration (r = -0.30; P less than 0.01); however, there was no relationship between subject age and percentage imipramine unbound. Though alpha-1-acid glycoprotein concentration increases with advancing age, because only a small proportion of the variability is explained by age, with other undefined factors being more important, drugs predominantly bound to alpha-1-acid glycoprotein such as imipramine may not have a clinically or statistically significant change in protein binding with increasing age in the absence of overt clinical illness.