We had previously shown that human T-lymphocytes (ERFC) that had been activated for a short time with phytohemagglutinin (PHA) produced positive inotropic and chronotropic effects on spontaneously beating rat atria (Sterin-Borda, L., et al., Naunyn Scmiedeberg's Arch. Pharmacol. 324, 58, 1983). In this study, we first prepared T4-rich (T4) and T8-rich (T8) cells from ERFC by selective lysis with OKT4 and OKT8 monoclonal antibodies and rabbit complement. Then, we tested the effect of PHA-stimulated T4 (PHA-T4) and T8 (PHA-T8) on beating rat atria. PHA-T4 cells stimulated the tension and the frequency of contraction of isolated rat atria by a mechanism that involved the generation of the slow reacting substance of anaphylaxis (SRS-A), since both 10(-5) M nordihydroguaiaretic acid (NDGA) and 10(-7) M FPL-55712 were effective inhibitors. On the other hand, PHA-T8 cells decreased the tension of beating atria. Indomethacin (10(-6) M) could not block the depressor effect. Cell-free PHA-T4 supernatants reacted with the heart tissue similarly to whole PHA-T4 cells. Since NDGA or FPL-55712 treated organs did not respond to active PHA-T4 supernatants, the lipoxygenase system of the auricles seems to be required for the reaction and the active metabolites appear to derive mainly from the heart. Our results suggest that PHA-activated "helper/inducer" cells release soluble factors that can in turn trigger the lipoxygenase metabolic pathway of arachidonic acid in the heart, generating the active leukotrienes responsible for the positive inotropic and chronotropic effects.