A secreted MUC1 mucin from the spent medium of the colon carcinoma cell line COLO 205 carrying sialyl‐Lewis a and x epitopes (H‐CanAg) was purified by trichloroacetic acid precipitation and Superose 6 gel filtration. The purified H‐CanAg inhibited adhesion of the leukocyte cell line HL‐60 to E‐selectin transfected COS‐1 cells or interleukin‐1β (IL‐1β)‐activated human umbilical vein endothelial cells. Sera from two patients with advanced colon carcinoma containing high concentrations of sialyl‐Lewis a and x activity inhibited HL‐60 cell adhesion to E‐selectin‐expressing COS‐1 cells and IL‐1β‐activated endothelial cells. After affinity column absorption of the sialyl‐Lewis a activity, the sera also lost most of their sialyl‐Lewis x activity and at the same time their adhesion inhibitory effect. A large part of the sialyl‐Lewis a/x activity in the two patients was found in fractions containing mucins having a MUC1 apoprotein, as shown by its size, and reactivity with the two anti‐MUC1 apoprotein monoclonal antibodies, Ma552 and HMFG‐2. The cell‐adhesion inhibitory effect of the purified sialyl‐Lewis a‐carrying MUC1 mucin fraction from the sera of the two patients was stronger than that of smaller sized sialyl‐Lewis a‐carrying mucin‐type glycoproteins also found in the patient sera. The MUC1 mucin fraction secreted by the COLO 205 cells and from the two sera were all shown to lack their C‐terminal portion, in contrast to the MUC1 mucin from cells. It is hypothesized that sialyl‐Lewis a‐ and/or x‐containing mucins, especially MUC1, secreted by tumors can interact with E‐selectin on endothelial cells and thus inhibit leukocyte adhesion. © 1996 Wiley‐Liss, Inc.