Cats are known to develop a lupus-like syndrome similar to that observed in humans when treated with propylthiouracil. We have previously demonstrated that propylthiouracil and other drugs associated with lupus are oxidized in the presence of myeloperoxidase to reactive intermediates. We postulated that these reactive metabolites could modify myeloperoxidase resulting in anti-myeloperoxidase antibodies and possibly be responsible for the lupus-like syndrome. Five cats were treated with propylthiouracil and 2 developed the lupus-like syndrome as well as anti-myeloperoxidase antibodies. These appeared to correlate better with disease than antinuclear antibodies. The antibodies were true autoantibodies because the myeloperoxidase used to detect the antibodies did not require treatment with propylthiouracil. In a subsequent study in which the cat food contained a higher level of taurine, none of the animals developed the autoimmune syndrome. It is possible that diet also plays an important role in the development of such adverse reactions.