Altered gene expression during breast tumour progression can occur through alternative splicing of mRNAs. The SR proteins have been identified as important factors in RNA splicing and in the incorporation of alternative exons in experimental systems. We have studied SR protein expression by western blot in human breast cell lines and in a cohort of 101 invasive breast tumours to examine the relationship with alternatively spliced isoforms of the CD44 gene. Multiple SR proteins (SR75, 55, 40, 30) were expressed in most cell lines and tumours, and their relative expression was independent of grade, size, or nodal status. Higher relative expression of SR55 protein was associated with an altered pattern of CD44 variants incorporating exon v7 (p = 0.047) as determined by reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis. Nevertheless, transient transfection of MCF7 and HBL100 breast cell lines with SR55 had no direct effect on the expression of CD44 v7 variant expression. We conclude that while SR proteins may be important and necessary factors in mRNA splicing, other factors are also necessary to influence the regulation of alternatively spliced isoforms of CD44.