Leukocyte adhesion deficiency II (LAD II), also known as congenital disorder of glycosylation IIc (CDG-IIc), is a human disease in which a defective GDP-fucose transporter (SLC35C1) causes developmental defects and an immunodeficiency that is based on the lack of fucosylated selectin ligands. Since the study of in vivo leukocyte trafficking in patients with LAD II is experimentally limited, we analyzed this process in mice deficient for Slc35c1. We found that E-, Land nd P-selectin-dependent leukocyte rolling in cremaster muscle venules was virtually absent. This was accompanied by a strong but not complete decrease in firm leuko-cyte adhesion. Moreover, neutrophil migration to the inflamed peritoneum was strongly reduced by 89%. Previous reports showed surprisingly normal lym-phocyte functions in LAD II, which indicated sufficient lymphocyte trafficking to secondary lymphoid organs. We now found that while lymphocyte homing to lymph nodes was reduced to 1% to 2% in Slc35c1 / mice, trafficking to the spleen was completely normal. In accordance with this, we found a defect in the hu-moral response to a T cell-dependent an-tigen in lymph nodes but not in the spleen. Taken together, Slc35c1 / mice show strongly defective leukocyte trafficking but normal lymphocyte homing to the spleen, which may explain normal lym-phocyte functions in LAD II. (Blood. 2008;