Objectives[ Since plasma protein binding of tricyclic antidepressants may be relevant to treatment e}ects and can be in~uenced by age!associated factors\ we examined both plasma ultra_ltrate and total concentrations of nor! triptyline "NT# in patients and compared these to age [ We hypothesized negative associations with age of both ultra_ltrate NT and the ratio of ultra_ltrate NT to total plasma NT[ Methods[ Patients with major depression at a psychiatric service treated with a stable dose of NT were studied[ Trough plasma ultra_ltrate NT concentrations and total plasma NT concentrations were measured by high per! formance liquid chromatography[ Concentrations were corrected for dose[ Results[ Eighty!seven patients aged 15ร77 years were studied[ Ultra_ltrate NT concentrations and the ratio of ultra_ltrate NT to total NT concentrations were both signi_cantly negatively associated with age[ Total NT con! centrations were not signi_cantly associated with age[ Conclusions[ Relatively low ultra_ltrate NT concentrations in older patients may re~ect lower tissue exposure at a given total plasma NT concentration[ This could be relevant to toxic and therapeutic e}ects[ Studies of relationships between non!bound drug concentrations and NT treatment outcomes across the age span are needed[ Copyright