The local effects of synthetic leukotrienes (LT) were examined in the skin of the anesthetized pig. Blood flow was measured noninvasively with the use of a laser-Doppler flow meter and changes in vascular permeability were measured using technetium-labeled human serum albumin as a marker for extravasation. LTB4 and the peptidolipid leukotrienes, LTC4, LTD4, LTE4, LTF4, induced vasodilator responses when injected intradermally at a dose of 1 ng. The vasodilator effects of LTB4 and LTF4 were comparable in magnitude to those of prostaglandin E2 (PGE2) and histamine and persisted over a wide dose range. Vascular permeability was induced by histamine, PGE2, and LTB4 but not by the other leukotrienes. The effects of LTB4 were significantly increased in the presence of PGE2. Leukotrienes appear not to produce their effects through the generation of prostaglandins as neither the vasodilator nor the permeability-enhancing effects were affected by treatment with indomethacin. The present investigation demonstrates that the pig is the first animal model to be described which reflects the potent vasodilator actions of leukotrienes in human skin. The porcine skin may thus be a useful model in the study of human skin diseases.