Pretreatment with complete Freund’s adjuvant blended with aluminium hydroxide (ALU-CFA) prevents the clinical as well as histological manifestation of experimental allergic encephalomyelitis (EAE) in Lewis rats. Suppression of prostaglandin biosynthesis with the cyclooxygenase inhibitor piroxicam (10 mg/kg body weight) from day 2 before to day 17 after EAE induction could not restore responsiveness in pretreated animals. In contrast piroxicam increased ALU-CFA-induced suppression of autoantibodies against myelin basic protein. In controls not pretreated with ALU-CFA, clinical signs of EAE were attenuated by piroxicam, whereas mononuclear infiltration of the brain remained unchanged. Therefore it is unlikely that prostaglandins exert an important function in the regulation of immune responses in this model of autoimmunity.