Changes in CD44 transcripts have been previously found to be associated with metastasis in animal models. The purpose of this study was to investigate CD44V changes in four well established high grade human brain tumor cell lines, known to possess prominent invasive behavior. In Northern blot analysis, CD44S and CD44V were expressed strongly in three high-grade glioblastoma multiforme cell lines (GBM 8401, GBM 8909, GBM 8804) and one malignant meningioma cell line (IOMM). By RT-PCR and blot hybridization, three variant transcripts (650 bps, 850 bps, and 1,000 bps) were detected in GBM 8804 and two isoform transcripts (650 bps, 850 bps) were recognized in GBM 8401 and 8909. Further, in a malignant meningioma cell line (IOMM), only one weak isoform (650 bps) was detected. However, by Northern blot analysis, neither CD44S or CD44V could be expressed in normal brain and meningeal tissue. These results indicate that discrete CD44 mRNA splice variants are expressed in high grade glial cell tumors and malignant meningioma and suggest a possible role in the invasion of malignant brain tumors.