Intravenous injection of leukotriene C4 (1 nmol X kg-1) caused substantial plasma exudation in anesthetized guinea pigs, as evidenced by marked hemoconcentration 15% in 5 min) and significant extravasation of Evans blue. Fluorometric quantitation of Evans blue content in 38 selected tissues documented that leukotriene C4 caused significant plasma extravasation throughout the body, except for the brain, stomach, duodenum, colon and gonads. In particular, the respiratory and the uro-genital tracts, but also the conjunctiva, the esophagus, the bile ducts and the umbilical ligaments, were very sensitive to the edema-promoting effect of leukotriene C4. Intravenous injection of leukotriene D4 (1 nmol- X kg-1) or E4 (5 nmol X kg-1) evoked plasma extravasation with a distribution and magnitude that was similar to that induced by leukotriene C4. It is concluded that the three major constituents of slow reacting substance of anaphylaxis (SRS-A), leukotrienes C4, D4 and E4, cause a generalized and extensive plasma exudation that is consistent with the proposal that these leukotrienes are important mediators of inflammation.