The effect of interferon-gamma on indoleamine 2,3-dioxygenase, a tryptophan catabolizing enzyme, was studied in cultured human placental chorionic villi. The activity of indoleamine 2,3-dioxygenase was markedly stimulated by interferon-gamma in a time- and concentration-dependent manner. Interferon-alpha and interferon-beta also showed a slight stimulatory effect on indoleamine 2,3-dioxygenase activity. The level of indoleamine 2,3-dioxygenase mRNA expression (determined by reverse transcription-polymerase chain reaction) was also enhanced by interferon-gamma. Interleukin-4 showed a dose-dependent inhibitory effect on interferon-gamma-induced stimulation of indoleamine 2,3-dioxygenase activity and mRNA expression.