Indoleamine 2,3-dioxygenase (IDO), one of the enzymes of tryptophan catabolism, has been shown to play an essential role for successful pregnancy through the inhibition of allogenic fetus-induced T-cell proliferation, and interferon-gamma (IFN-gamma) induces the expression of IDO in CD14-positive (CD14(+)) cells. On the other hand, prolactin (PRL) is the hormone whose serum levels drastically elevate during pregnant period and is shown to play an important role in the early stages of pregnancy including implantation. However little is known about the physiological significance of the elevation of PRL from second trimester except for its fundamental role in lactation. Since receptors of PRL and IFN-gamma share their structure and the signal transduction pathway, we hypothesized the potential crosstalk between two substances. To test this idea, we examined the effect of PRL on IFN-gamma-induced IDO expression in CD14(+) cells. CD14(+) cells were prepared from peripheral blood of 12 healthy controls who had informed consent, and IDO expression and transcriptions were analyzed by flow cytometry and RT-PCR. The results showed that although PRL by itself had little effect on IDO expression, PRL significantly enhanced the IFN-gamma-induced IDO expression at comparable to those seen in a pregnant period. In contrast, no such effect was observed with PRL at lower concentrations comparable to those seen in a non-pregnant period. These findings suggest that PRL may contribute to the maintenance of pregnancy by augmenting IFN-gamma induction of IDO expression.