CD44 is a cell-surface glycoprotein postulated to play a role in tumor-cell metastasis. We have examined the expression of the standard CD44 (CD44s), and alternative spliced variants of CD44 containing variant exons v6, v9, and v1O (CD44v6, CD44v9, and CD44v10 respectively) in 9 samples of normal cervix, 6 samples of cervical intraepithelial neoplasia (CIN), and 11 samples with invasive cervical carcinomas. RT/PCR demonstrated the presence of CD44s in all samples of normal cervix and those with invasive carcinomas. CD44v6 was also found in all normal cervical samples and in 9 tissue samples of invasive carcinomas. The results also suggested that some tumor specimens had several higher molecular transcripts containing exon v6 compared to specimens of normal cervix. Immunohistochemistry detected the presence of CD44s and the absence of CD44v10 in both epithelial and stromal cells in all specimens. In contrast, CD44v6 and CD44v9 were stained positive in epithelial cells but were absent in stromal cells. The intensity of CD44v6 and CD44v9 staining was strongest in normal cervical epithelium followed by CIN, invasive squamous cell carcinoma, and adenocarcinoma. In the malignant samples, heterogeneity in staining intensity among different clusters of tumor cells was observed. Furthermore, poorly differentiated and undifferentiated carcinomas from patients having poor prognosis did not stain at all. This study suggests that variant CD44 molecules may serve an important function in the cell contact of cervical epithelial cells, and that cervical epithelium acquires heterogeneity in the expression of CD44 adhesion molecules during carcinogenesis, which may be related to tumor metastasis.