The activity of an alpha 2,6 sialyltransferase acting on N-acetyllactosaminic sequences (alpha 2,6 ST E.C. 2.4.99.1) has previously been found to be increased in 90% of human colon cancer specimens. In the present study, the alpha 2,6 ST activity of 6 human colon cancer cell lines grown in culture was compared with that expressed by the corresponding nude mice xenografts and by the cell lines derived from the xenografts. We found that xenografts of COLO 205, HT-29, SW 620, SW 948 and SW 948 FL (a non-adherent sub-line of SW 948) cells express an alpha 2,6 ST activity much higher than that of the in vitro-grown cells. SW 48 cells grown either in culture or as xenografts lack the enzyme activity. All the xenograft-derived cell lines except HT-29 retained the increased alpha 2,6 ST activity at least for the first 6 passages. Those derived from SW 948 xenografts showed an enrichment of round, non-adherent cells, strongly reactive with the NeuAc alpha 2,6 Gal/GalNAc-specific lectin from Sambucus nigra (SNA), thus indicating that a selection of these cells has occurred.