A human glioma cell line, SA146, was initiated on precoated extracellular matrix from a stereotactic biopsy of a glioblastoma. We report modulation in the expression of glial fibrillary acidic protein (GFAP) by SA146 passed in vitro before or after xenogenic transplantation into nude mice. Immunofluorescence data show a decrease in the percentage of GFAP-expressing cells with increasing in vitro passages but a full reexpression (100% of GFAP-positive cells among vimentin-positive cells) was observed in cultures just derived from the xenotransplanted tumor. These changes are correlated with the mRNA content (Northern blot probed with a cDNA for GFAP) and with the protein level (cytoskeletal fraction analyzed by two-dimensional gel electrophoresis and Western blots probed with a monoclonal antibody). At the optimal level of GFAP expression, a large range of micro-heterogeneity in GFAP isoforms is reached for which post-translational events are clearly involved since mRNA translation in cell free system would provide at best three isomers. We suggest that SA146 would be an appropriate model to study the regulation of GFAP expression in the context of human glial tumor biology.