A dual isolated organ technique comprised of a guinea-pig lung parenchymal strip and a guinea-pig ileum was used to determine if slow reacting substance of anaphylaxis (SRS-A) is released from parenchyma during contractions evoked by antigen (ovalbumin) or by ionophore (A23187). An immunologically sensitized parenchyma served as the primary target organ for ovalbumin and either a sensitized or unsensitized parenchyma was the target tissue for A23187; an unsensitized ileum functioned as the assay organ. In the presence of pyrilamine and indomethacin, ovalbumin or A23187 produced contractions of the parenchyma and concomitantly caused release of SRS-A from the lung strip which was indicated by a contraction of the ileum. The ileal response was antagonized by FPL 55712, whereas the parenchyma contractions were unaffected. Additional experiments were conducted in which parenchyma was contracted with histamine. At the height of the histamine contraction, the bathing fluid surrounding the parenchyma was removed and assayed on a pyrilamine-treated ileum. SRS-A was not detected, indicating that SRS-A release from parenchyma is not a function of tissue contraction per se, but is related to the antigen- and ionophore-induced contractions. To explain the lack of effect of FPL 55712 on parenchymal contractions to antigen or ionophore, we compared the degree of antagonism produced by FPL 55712 on SRS-A contraction of parenchyma and ileum. These experiments indicated the possibility that at least two different classes of SRS-A receptors exist and that those in the ileum and lung differ.