LTD4 and PGE2 crosstalk causes a synergistic increase in PGD2 secretion and Erk phosphorylation and is mediated through PKG and Erk. LAD2 cells were stimulated with 0.5 μmol/L LTD4, 0.5 μmol/L PGE2, or both in the presence or absence of MK571 (1 μmol/L), L-798 (100 nmol/L), KT5823 (KT; 5 μmol/L), or PD98059 (PD; 50 μmol/L) before treatment, and PGD2 secretion (A and F), Erk phosphorylation (B), c-fos (C and D), and MIP-1β generation (E) were analyzed. *P < .05, **P < .01, and ***P < .001.