Using a well-defined in vitro model system for neoplastic progression, we have examined two basic characteristics in the acquisition of amplification potential. Since Syrian hamster embryo fibroblasts can be transformed by a variety of methods (spontaneously, chemically, virally, or by transfection with oncogenes), we determined whether the method of transformation affects the capability of a cell to amplify. In addition, since variants can be isolated from cell populations as they progress toward tumorigenicity, we can monitor changes in amplification potential during this multistep process. We find that the capability to amplify is independent of the method of transformation and that the acquisition of this ability occurs in a defined step in the transformation process. In this model system, acquisition of amplification ability occurred concomitantly with the loss of tumor suppression function.