This investigation reports the effects of various terminal procedures, and how they modified the responses to a toxicant (polychlorinated biphenyls [A1254], 130 mg/kg/day × 5 days) administered by gavage to Sprague-Dawley male rats. Terminal procedures included exsanguination via the abdominal aorta under anesthesia (isoflurane inhalation or Equithesin injection), decapitation with or without anesthesia, or narcosis induced by carbon dioxide inhalation. Effects of repeated anesthesia were also tested. Terminal procedures induced confounding stress responses, particularly when Equithesin was used. The terminal procedures modified the conclusions about effects of A1254 on the concentrations of corticosterone, insulin, glucagon, glucose, alkaline phosphatase, lactate dehydrogenase, uric acid, and blood urea nitrogen, from nonstatistically significant to significant changes, and in the case of luteinizing hormone from a statistically significant increase to a significant decrease. Investigations of effects of toxicants should be designed and interpreted considering potential changes induced by the selection of a terminal procedure.