By targeted disruption of the MIF gene, we have established a mouse strain deficient in macrophage (Mφ) migration inhibitory factor (MIF). Despite previous reports indicating an essential role of MIF in endotoxaemia, an injection of lipopolysaccharide (LPS) into the MIF‐deficient mice (maintained under specific pathogen‐free conditions) caused shock. No significant difference was detected between the MIF‐deficient mutant and normal mice in susceptibility to LPS for endotoxaemia or tumour necrosis factor‐α (TNF‐α) formation upon LPS injection. Peritoneal Mφ from the two strains produced TNF‐α in response to LPS with similar dose responses. Dexamethasone suppressed the LPS‐induced TNF‐α response of Mφ, but no difference was detected between the Mφ from the two strains. These results suggest that endogenous MIF has no significant effect on the LPS‐induced TNF‐α production and no effect on suppression of the response by glucocorticoids. Thus, MIF is not crucial for LPS‐induced immune responses leading to shock.