The use of Terramycin (TM-100F), a feed premix containing the broad spectrum antibacterial agent oxytetracycline (220 g/kg), is being extended to control columnaris infections caused by Flavobacterium columnare in cool- and warmwater fish. The study objective was to determine the safety of oxytetracycline administered in feed to walleye Stizostedion vitreum, yellow perch Perca flavescens, and hybrid striped bass Morone saxatilis x M. chrysops. The presently approved oxytetracycline treatment regimen is 55 to 82.5 mg/kg bodyweight (BW)-1d-1 for 10 d. Nominal oxytetracycline dose rates evaluated were 0 (control), 82.5, 248, or 413 mgkg BW-1d-1 offered for 10 (yellow perch and hybrid striped bass) or 20 consecutive days (walleye). Parameters evaluated included daily mortality, behavioral observations (appetite, distribution, and flight/fright response), water chemistry observations, initial and terminal weight measurements, and gross and microscopic pathology. Yellow perch and hybrid striped bass consistently consumed 50 % to 100% of the diet offered during dosing. Although walleye feed consumption was occasionally less than 50% of the diet offered, feed or fecal material was present in the gastrointestinal tract of all necropsied walleye except for one control fish. There were no oxytetracycline-related mortalities or clinically observable changes in behavior for any of the species tested. Oxytetracycline-related changes were limited to growth and histopathology data. The single oxytetracycline-related growth effect was that hybrid striped bass offered a nominal dose of 413 mgkg BW-1d-1 were significantly smaller than untreated controls at the terminal sampling. Oxytetracycline-related histopathological findings were limited to walleye, and these findings included decreased hematopoietic/lymphopoietic (H&L) tissue in the anterior kidneys, diffuse hyperplasia of the gill filament epithelium, and a decreased prevalence of fish with eosinophilic droplets in their renal tubular epithelial cells. Although the incidence of decrease H&L tissue tended to increase in proportion to the oxytetracycline dose, this finding was only statistically significant for fish that received a nominal dose of 413 mgkg BW- 1d-1. All three microscopic findings were of low severity, and their mechanism with regard to oxytetracycline administration remains undetermined. Given the pathogenicity of the types of bacteria controlled by oxytetracycline treatment, the long history of its use in major aquaculture species, and the relatively minor treatment-related effects in walleye and hybrid striped bass, the relative risks of oxytetracycline treatment are probably outweighed by its disease control benefits.