Cell-mediated immunity and macrophage activity, especially that of Kupffer cells, are impaired during cholestasis. Some evidence exists that bile acids play a role in these immune defects. The purpose of this study was to evaluate the effects of individual bile acids on immunity and to determine whether monocytes could be a target. We assessed the effects of chenodeoxycholic acid, an endogenous bile acid, ursodeoxycholic acid, which has been shown to partially correct the immunological abnormalities observed in primary biliary cirrhosis, and their tauroconjugates on the production of interleukin-1, interleukin-6 and tumor necrosis factor-or. Chenodeoxycholic acid had a dosedependent inhibitory effect on interleukin-1 (inhibitory concentration 50% = 60 pmoUL), interleukin-6 (inhibitory concentration 50% = 80 pmoUL) and tumor necrosis factor-a (inhibitory concentration 50% = 80 pmolb) production; inhibition was almost complete at 250 pmoUL. In contrast, ursodeoxycholic acid had lesser or minimal inhibitory effects (inhibitory concentration 50% = 100 pmol/L for interleukin-1 and above 200 pmoUL for interleukin-6 and tumor necrosis factor-a). The inhibitory effects of taurochenodeoxycholic acid and tauroursodeoxycholic acid were similar to those of chenodeoxycholic acid and ursodeowcholic acid, respectively. Ursodeoxycholic acid did not reverse the chenodeoxycholic acid-induced inhibition of interleukin-6 or tumor necrosis fact0F-a production. In conclusion, chenodeoxycholic acid exerts strong inhibitory effects on monOcyte activity in uitro, whereas the effects of ursodeoxycholic acid are minor. (HEPATOLOGY 1992;16:719-723.) Cell-mediated immunity (1-3) and macrophage activity, especially that of Kupffer cells (4,5), are impaired during cholestasis, an observation that may be related to the onset of severe systemic infections in this setting (6, 7). Indeed, bile acids have immunosuppressive properties on cell-mediated immunity and macrophage ac-