The potential aquatic fate of oxytetracycline (OTC) in streams receiving discharge from fish hatcheries was examined using the Water-Quality Analysis Simulation Program (WASP, Ver 6.1) model. The modeled 4.4-km stream network included a settling pond, a receiving segment, and two downstream segments. Attainment of quasi-steady state concentrations (concentration variation, <7.5 mg kg−1) in the sediment layers of the receiving segment and first downstream segment required several years. Median water-column concentrations (truly dissolved and colloid- and particle-associated) were 0, 0.57, 0.80, and 0.83 ng L−1 in the settling pond, receiving segment, first downstream segment, and second downstream segment. Truly dissolved fractions in the water column during dosing were 16% in the settling pond, 64% in the receiving segment, and approximately 78% in the river segments. Concentrations declined 20- to 400-fold, depending on the segment considered, within 1 d of dosing. Truly dissolved fractions in the water column after cessation of dosing were 96% in the settling pond and approximately 78% in the river segments. Expected sediment-bound concentrations were approximately 4 mg kg−1 in the receiving segment during dosing, with a median annual concentration of approximately 1.5 mg kg−1. Expected concentrations in downstream sediments were 0.2 mg kg−1 or less. Sensitivity analyses indicated the most important factors influencing fate under the hydrodynamic conditions simulated were settling-pond biosolids load, biosolids settling velocity, OTC depuration kinetics from biosolids, and OTC river particle-water distribution coefficient(s).