AbstractWe investigated cytoplasmic control of tumorigenicity in cybrids. Cytoplasts derived from nontumorigenic cells were fused to the highly tumorigenic 984 Cl 10–15 cell line derived from a murine teratoma. The resultant cybrids did not retain the tumorigenicity of the original cell line. In addition, the majority demonstrated the ability to differentiate into skeletal muscle. The results of these experiments indicate a heritable suppression of the tumorigenic phenotype by nontumorigenic cytoplasm. These findings are in contrast to our previous experiments in which we used a different experimental system and demonstrated a nuclear control of tumorigenicity in cybrids.