Changes of tropomyosin isoforms have previously been found accompanying morphologic alterations such as those associated with neoplastic transformations in mammalian cells. To determine whether an isoform change is associated with the malignancy of brain tumors, we employed both polyclonal antibodies specific to high and low molecular weight tropomyosin isoforms. We found, by using immunocytochemistry and immunoblotting, that an alteration of tropomyosin isoforms is associated with human astrocytomas. Differential staining patterns were seen for normal, reactive, and neoplastic astrocytes. Characterization of the antibodies revealed an increase in the higher molecular weight tropomyosin in more anaplastic astrocytomas than in those that were well differentiated. We also observed that the different isoforms have specific subcellular localizations. These findings suggest that neoplastic transformation is associated with alteration of tropomyosin isoforms in astrocytomas. We speculate that this change may be related to morphologic transformation in which microfilament functions, such as cell shape, interaction, and recognition are altered.