Male rats were treated with subcutaneous vehicle or 16, 16-dimethyl-PGE2 (dmPGE2, 100 μg per kg), 24,18 and 0.5 hr prior to and 6, 24 and 30 hr after challenge with oral α1-napthylisothio-cyanate (ANIT, 30 mg per kg). Forty-eight hours after challenge, rats were sacrificed by decapitation; serum and liver samples were taken for biochemical and histological analysis, respectively. Rats treated with vehicle (2% ethanol in saline) and ANIT exhibited elevations in alkaline phosphatase, SGPT and bilirubin as well as cholangitis and mild parenchymal necrosis. Rats treated with dmPGE2 and ANIT had normal serum biochemical findings, no necrosis and only mild proliferation of bile duct epithelium. Thus, dmPGE2 may be able to protect the rat liver against the deleterious effects of orally administered ANIT.