The mechanisms that mediate the recruitment of Th1 and Th2 lymphocytes in vivo are poorly understood. We demonstrate that the mechanisms by which exogenously produced CD4+ Th1 and Th2 cells roll and adhere in Con A-inflamed liver microcirculation differ dramatically: Th1 cells use α4β1-integrin and Th2 cells use the vascular adhesion protein (VAP)-1. P-selectin plays no detectable role in Th1 or Th2 cell trafficking in liver microcirculation. Cellular recruitment in the liver sinusoids has previously been shown to be independent of many known adhesion molecules, leading to the suggestion that recruitment in these structures is mediated by physical trapping. While this may still be true for neutrophils, Th1 and Th2 cells use α4-integrin and VAP-1, respectively, to adhere within the liver sinusoids.