Background/Aims: Leukotriene A<sub>4</sub> (LTA<sub>4</sub>) hydrolase catalyzes the final step in the synthesis of leukotriene B<sub>4</sub> (LTB<sub>4</sub>). TH-1- and TH-2-derived cytokines may regulate LTB<sub>4</sub> synthesis by monocytes through their actions on the expression of LTA<sub>4</sub> hydrolase. Methods: Freshly isolated monocytes were incubated with pro- and anti-inflammatory cytokines for 36 h. mRNA expression was determined by Northern blot, protein expression was determined by Western blot and LTB<sub>4</sub> synthesis was determined by ELISA. Results: Interferon-γ (a TH-2-derived cytokine) increased significantly LTA<sub>4</sub> hydrolase mRNA expression, whereas interleukin (IL)-4 and IL-13 (both TH-2-derived cytokines) decreased LTA<sub>4</sub> hydrolase mRNA expression in these cells. The same effects were seen on the expression of immunoreactive LTA<sub>4</sub> hydrolase after incubating the monocytes with either TH-1- or TH-2-derived cytokines. The monocyte-derived cytokine IL-1β did not show any significant effect on LTA<sub>4</sub> hydrolase mRNA expression. When LTB<sub>4</sub> release was measured, both IL-1β and interferon-γ significantly increased LTB<sub>4</sub> production by monocytes, while TH-2 cytokines (IL-4 and IL-13) decreased it. Conclusion: The opposing effects of TH-1- and TH-2-derived cytokines on the expression of LTA<sub>4</sub> hydrolase mRNA may regulate LTB<sub>4</sub> synthesis by monocytes during inflammation.