Cytokines are recognized to play an important role in modulating the immune and neuroendocrine system. We recently reported leukemia inhibitory factor (LIF) increased ACTH secretion and pro-opiomelanocortin mRNA level in the murine corticotroph tumor cell line (AtT-20). In this study, the expression of LIF in normal rat pituitary could be demonstrated by ribonuclease protection assay. LIF (1 nM) caused a slight, but significant increase in ACTH secretion (43.7% increase versus control, P<0.01), while showing statistically no significant change of growth hormone and prolactin level in dispersed rat pituitary cells. CRH (10 nM) also induced ACTH secretion 2.5-fold (P<0.01), and co-treatment of LIF and CRH exhibited 2.8-fold increase of ACTH secretion but no statistical difference from CRH treated group. These findings suggest that LIF also has same enhancing effect of ACTH secretion in primary pituitary cultured cells of rat as in AtT-20 cell and LIF acts as a paracrine or autocrine factor to modulate neuroendocrine function in the pituitary.