To understand the relationship between CD44 gene expression and an established variable associated with aggressive behaviour in human breast cancer, we have studied a panel of 6 breast cell lines and 40 breast tumors selected primarily on the basis of estrogen receptor (ER) status. CD44 (standard form) mRNA was assessed by semi-quantitative RT-PCR, and CD44 variants incorporating exon v7 or v10 were studied by RT-PCR and Southern blot. While CD44 expression was not influenced by estrogen in ER+ve MCF-7 cells. CD44s expression was slightly higher (up to 2 fold) in ER-ve cells but there was a marked decrease in the range of CD44 variants incorporating exons v7 or v10. In microdissected tumors, the levels of CD44s showed no correlation with ER status but the pattern of expression of larger forms of CD44 incorporating variant exons v7 and v10 was significantly different (p = 0.005 and p = 0.015, respectively) between ER+ve and ER-ve tumors, reflecting the pattern seen in the cell lines. These findings suggest that the profile of CD44 expression in breast cancer may reflect cellular differentiation as indicated by the ER phenotype. The influence of these differences in CD44 expression on the increased metastatic potential of ER negative breast cancer remains to be determined.