The current study analyses the effect of PRL, a hormone involved in numerous physiological processes, on dendritic cells (DC) of rat thymus. Most thymic DC express prolactin receptors (PRL-R) as demonstrated by both immunohistochemistry and flow cytometry. PRL administration during 2 or 6 days to fetal thymus organ cultures (FTOC) does not increase the proportions of DC in cultures but stimulates their differentiation. Furthermore, PRL-treated thymic DC exhibit increased allostimulatory capacity in mixed leukocyte reaction (MLR) assays in association with increased surface expression of both MHC antigens and the co-stimulatory molecule CD80. PRL-treated DC also produce increased amounts of pro-inflammatory cytokines, such as IL-12, TNFalpha and IL-1beta, but not of IL6 or IL-10. Our data suggest a key role for IL-12 in the observed changes in the allostimulatory capacity of PRL-treated DC. Also, they permit us to hypothesize about the physiological role played by PRL in thymus ontogeny.