CD11c⁺ (F4/80^– CD68^–) dendritic cells (DC) in the colonic lamina propria (cLP) of normal and immunodeficient (RAG1^–/–) C57BL/6 (B6) mice show high surface expression of MHC class I/II molecules and CD1d, and low surface expression of CD40, CD80, CD86 costimulator molecules. CD4⁺ α β T cells from normal or MHC class II‐deficient B6 micetransferred into congenic RAG1^–/– hosts induce a progressive, lethal colitis. Concomitant with colitis development, DC in the inflamed cLP increase in number and up‐regulate surface expression of CD1d, MHC class II molecules and CD40, CD80, CD86 costimulator molecules. cLP DC from non‐transplanted (healthy) and transplanted (diseased) mice produce similar amounts of IL‐12 p70 and IL‐10 in response to CD40 signaling, but the inducible IL‐12 p40 release is 5–15‐fold higher in mice with colitis than in non‐transplanted mice. Binding of IL‐12 p40 to p19 generates IL‐23. Freshly isolated cLP lymphocytes (cLPL) from transplanted, diseased mice express 3–10‐fold more p19 transcripts than cLPL from non‐transplanted, healthy mice. p19 expression by cLPL is further up‐regulated in response to CD40 ligation. Freshly isolated cLP DC from transplanted mice with colitis (but not from non‐transplanted controls) stimulate IFN‐γ (but not IL‐4 or IL‐13) release by co‐cultured NKT cells. Incolitis, DC accumulate in the cLP, show an activated surface phenotype, up‐regulate IL‐12 p40 and p19 expression, and ‘spontaneously’ stimulate NKT‐like cells. cLP DC may be interesting targets for novel therapeutic approaches to modulate mucosal T cell responses in situ.