The production of IL‐12 by dendritic cells (DC) early in an immune response is considered critical for the polarization of CD4⁺ T lymphocyte response towards a Th1 pattern, a key process in the clearance of intracellular pathogens. Infection of bone marrow‐derived DC with Mycobacterium bovis Bacillus Calmette Guérin (BCG) induced a concurrent and dose‐dependent releaseof IL‐10 and IL‐12. Here we examined whether the production of IL‐10 by DC affected their IL‐12 response to mycobacterial infection and the generation of protective immune responses in vivo. Compared to wild‐type (WT) DC, DC deficient for IL‐10 synthesis (IL‐10^–/–) showed increased IL‐12 production in response to BCG infection and CD40 stimuli in vitro. Moreover, when transferred into mice, infected IL‐10^–/– DC were more efficient than WT DC at inducing IFN‐γ production to mycobacterial antigens in the draining lymph nodes (DLN).This effect was associated with increased trafficking of IL‐10^–/– DC to the DLN and enhanced IL‐12 production by DC within the DLN. These data show that autocrine IL‐10 exerts a dual inhibitory effect on the induction of primary immune responses by DC: first, by down‐regulating the migration of infected DC to the DLN and second, by modulating the IL‐12 production by DC in the DLN.