There is increasing evidence that the expression of variants of the glycoprotein CD44 is related to the invasive and metastatic potential of tumour cells. By in situ hybridisation, we analysed the cellular expression of human homologues of a rat metastasis-associated CD44 variant v6 in invasive and non-invasive colorectal neoplasia and normal colonic mucosa. No specific hybridisation signals could be detected in epithelial cells of the normal crypt (n = 10). In contrast, we found moderate epithelial hybridisation signals in adenomatous polyps of mild dysplasia (n = 6). Adenoma cells of moderate or severe dysplasia (n = 7) showed increased hybridisation signals compared to mildly dysplastic adenomas (P < or = 0.01). We could not demonstrate significant differences in CD44v6 transcript levels between cells of dysplastic adenoma and primary adenocarcinoma (n = 11) (P > or = 0.05). Furthermore, we were not able to demonstrate a significant difference between primary and metastatic tumours (n = 7) (P > or = 0.05). However, there was a significant difference between metastatic carcinoma and adenomas with advanced dysplasia (P < or = 0.01). Our data demonstrate that significant transcriptional expression of CD44v6 is not confined to invasive tumour cells, but is already detectable in cells of adenomatous polyps showing mild dysplasia. The results of this study show a close relationship between cellular dysplasia and steady state levels of CD44 variant v6 transcripts in colorectal neoplasms.