The effect of immunologic hypersensitivity to a metabolite of halothane (trifluoroacetate) on the halothane-hypoxia-induction model was tested in mice and rats. Male Fisher 344 rats (200 g) were immunized with ovalbumin-trifluoroacetate (OVA-TFA) and the time course of the delayed hypersensitivity response determined. The animals had a peak response between 4 and 6 weeks after immunization. Rats were immunized with OVA-TFA, OVA, or saline 5 weeks before being anesthetized. Ten days before anesthesia, the animals were started on 0.1% phenobarbital in the drinking water. The animals were anesthetized with 1% halothane and 14% oxygen for 2 h. Hypersensitivity to TFA had no effect on the liver damage in either the mouse or the rat. These results do not rule out an immunologic vector in halothane hepatitis but make the involvement of TFA unlikely.