Effects of interleukin-4 (IL-4) and interferon-γ (IFN-γ) on rat Kupffer cell (KC) functions were investigated. Lipopolysaccharide (LPS)-stimulated KCs pretreated with IL-4 produced much more prostaglandin E2 than those pretreated with IFN-γ. In contrast, LPS-stimulated KCs pretreated with IFN-γ produced much more tumor necrosis factor-α, and nitrate and nitrite than those pretreated with IL-4. Different morphologic changes were induced after the culture with each cytokine; transformation of KCs into multinucleated giant cells with IL-4 was especially noted. These results suggest that IFN-γ and IL-4, produced by different subsets of T-helper lymphocytes, differently induce KC into specific morphology, and change KC response to endotoxins, possibly resulting in a modulation of hepatic inflammation.