The karyotypes of seven human glioblastomas were followed through serial subcutaneous passage in athymic mice. One tumor maintained the same hypodiploid stemline as seen in the original biopsy. Three tumors that originally had near-diploid stemlines showed an increase in stemline number to pseudodiploid or hyperdiploid due to gains of whole chromosomes. One tumor showed an entirely different karyotypic profile in the xenograft than had been demonstrated originally. Two tumors showed a shift from near-diploid stemlines to near-tetraploid and near-pentaploid stemlines. Structural abnormalities, including double minutes, that were present originally were maintained in the xenografts, and acquisition of new marker types was rare. Five of the seven lines showed an increased growth rate with serial passage as measured by a shortening of tumor doubling time and decreased time to 1000-mg size. There was, however, no obvious relationship between this change in growth rate and the karyotypic or histologic pattern. These studies demonstrate that most subcutaneous xenografts derived from malignant human gliomas retain karyotypes similar to those seen originally, making these systems useful models for studying the biologic significance of the chromosomal abnormalities of these tumors.