Amitriptyline and nortriptyline are widely used tricyclic antidepressant drugs. They have been detected in wastewater, surface runoff, and effluents from sewage treatment plants. As such, they could potentially reach agriculture land through the application of municipal biosolids or reclaimed water. In the absence of data on their fate in the environment, the persistence and dissipation pathways of radiolabeled amitriptyline were determined in three agriculture soils varying widely in texture and chemical properties (loam soil, clay loam soil, and sandy loam soil). Tritiated amitriptyline was added to laboratory microcosms containing soils, and the metabolism of the extractable (3) H was monitored during incubation at 30°C. The total solvent extractable radioactivity decreased in all three soils with times to dissipate 50% of material (DT50) ranging from 34.1 ± 3.2 (loam soil) to 85.3 ± 3.2 d (sandy soil). Nortriptyline (N-desmethyl amitriptyline) and amitriptyline-N-oxide were identified as major transformation products in all three soils by high performance liquid chromatography with photodiode array detector and time-of-flight mass spectrometry (HPLC-TOF-MS/UV). The addition of liquid municipal biosolids to the loam soil had no effect on the dissipation of amitriptyline. The persistence of nortriptyline was evaluated in the loam soil. The DT50 of nortriptyline was 40.5 ± 3.2 d estimated with HPLC-TOF-MS/UV. Approximately 10% of added nortriptyline was converted to hydroxylated products after 50 d of incubation. In summary, amitriptyline persisted in agricultural soils with major dissipation mechanisms, including forming nonextractable residues and producing various transformation products including the psychoactive drug nortriptyline.