We examined the effects of transforming growth factor-β (TGF-β) on the mRNA expression of the antioxidative enzymes, catalase, manganese superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (CuZnSOD), as well as the oxidative enzyme, xanthine oxidase (XO), in cultures of cardiomyocytes, cardiac non-myocytes, and fetal bovine heart endothelial cells. TGF-βs alone had little effect on expression of these enzymes, but treatment with a combination of interleukin-1β, interferon-γ, and tumor necrosis factor-α increased expression of MnSOD, catalase, and XO in some cell types with little effect on CuZnSOD expression. When TGF-βs were added along with these inflammatory cytokines there was a return to control levels of catalase expression, as well as a dramatic reduction in XO expression. In fetal bovine heart endothelial cells, treatment with inflammatory cytokines increased XO mRNA expression 11.5-fold and inclusion of TGF-βs reduced this 4-5-fold; effects on XO enzyme activity paralleled those seen on mRNA expression. Similar changes in XO expression were seen in cardiomyocytes. In contrast, TGF-βs did not change cytokine-induced MnSOD expression. All three mammalian isoforms of TGF-β showed similar effects. In summary, TGF-βs may be able to decrease superoxide anion production and subsequent tissue damage by decreasing levels of XO.