Alterations in expression of the CD44 adhesion protein have been implicated in colorectal tumourigenesis. Overexpression of variant high molecular weight isoforms (especially CD44v6), as well as down-regulation of standard CD44 (CD44s), are postulated to result in increased tumourigenicity. We studied the metastatic phenotype produced by the expression of CD44s by stable transfection into a human colorectal carcinoma cell line, SW620, that shows absence of any CD44 expression. Splenic injection of 2 x 10(6) SW620 colon cancer cells into SCID mice was used to produce hepatic metastases. The animals were sacrificed at 6 weeks after injection and morphological end-points relating to macrometastases and micrometastases were studied CD44s expression was associated with decreased development of macroscopic tumours (0.9 vs 3.0 tumours/ mouse liver, p = 0.004), less extensive tumour replacement of the liver (2.6% vs 12.8%, p = 0. 04) and decreased numbers of micrometastases (3.8 x 10(-8) vs 7.9 x 10(-8) micrometastases/ microm2, p = 0.2). This study is the first to demonstrate the mitigating effect of CD44s expression on the hepatic metastatic phenotype in a colorectal carcinoma cell line that does not ordinarily express CD44.