Indomethacin potentiates antigen-induced contraction and histamine release in lung parenchymal strips from ovalbumin-sensitized guinea-pigs. Mepyramine and the leukotriene antagonist FPL 55712 did not affect the potentiating effect of indomethacin on anaphylactic contraction, but two lipoxygenase inhibitors, BW 755C and nordihydroguaiaretic acid, abolished it. FPL 55712 inhibited contractile responses to leukotriene D4, but not those to leukotriene C4. The potentiation of histamine release by indomethacin was unaffected by the lipoxygenase inhibitors. It is concluded that a lipoxygenase product, possibly leukotriene C4, mediates the potentiation of contraction by indomethacin; the enhancement of histamine release, however, involves a different mechanism, possibly inhibition of the production of inhibitory prostaglandins.