The present study has identified the metabolites of arachidonic acid (AA) formed by the isolated frog cornea and has shown that this tissue is capable of the biosynthesis of both lipoxygenase and cyclo-oxygenase pathway metabolites. The cyclo-oxygenase (CO) metabolites found in greatest abundance were the prostaglandins E2 and F2a (PGE2 and PGF2a). The major lipoxygenase (LO) pathway metabolite found by thin-layer chromatography (TLC) was leukotriene B4 (LTB4), whereas leukotriene C4 (LTC4) biosynthesis was detected by radioimmunoassay. These leukotrienes (LTs) are highly potent modulators of active chloride transport, since incubation with LTC4 (10(-7)-10(-9) M) resulted in a dose-dependent stimulation of both the Cl- originated short-circuit current (SCC) and potential difference (PD). In contrast, LTB4 (10(-7)-10(-9) M) inhibited both of these parameters. Both LTC4 and LTB4 exerted these effects only when applied to the endothelial side. Preincubation with the leukotriene receptor antagonist, FPL 55712 completely blocked the response to LTC4, indicating that the action of LTC4 in the cornea is receptor-mediated. In this report the authors show that LTB4 and LTC4 are formed by the cornea and that they are potent modulators of the SCC and PD in chamber experiments. The possibility exists that LTB4 and LTC4 may function as endogenous regulators of net Cl- transport in the cornea, since the addition of these metabolites resulted in a dose-dependent stimulation (with LTC4), and inhibition (with LTB4), of both the short-circuit current (SCC) and potential difference (PD).