Dendritic cells (DC) can be obtained from peripheral blood mononuclear cells (PBMC) by in vitro culture with IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF). IL-13 shares properties with IL-4 but its receptor does not involve the common gamma chain present in the receptor complex of IL-4 and other cytokines. The present study was aimed to elucidate whether IL-13 can substitute for IL-4 in DC cultures and to compare the phenotypic and functional characteristics of cells obtained using these two cytokines. Monocyte-enriched PBMC were cultured with GM-CSF and IL-4 or GM-CSF and IL-13. Cell yields and DClike morphology were similar. The cells showed a membrane phenotype typical of DC (MHC II+; CD1a+; CD14-; CD3-; CD20-). IL-13-derived and IL-4-derived DC were similar in terms of macropinocytosis, stimulatory capacity of cord blood lymphocytes in mixed leukocyte reaction (MLR), and responsiveness to chemotactic signals. It is concluded that IL-13 is as effective as IL-4, combined with GM-CSF in sustaining DC differentiation from PBMC and that activation of the common gamma chain-driven transduction pathways is dispensable for DC differentiation and function.