The relative roles of nucleus and cytoplasm in the induction and maintenance of the malignant state were studied. Cytoplasmic hybrid (cybrid) clones, derived from the fusion of cytoplasts from malignantly transformed cells to normal whole cells, produced tumors in 17% of the animals injected with them. Nuclear/cytoplasmic hybrid (reconstituted cell) clones, derived by fusion of cytoplasts from malignant cells with karyoplasts of normal cells, produced tumors in 97% of the animals injected. A unique aspect of this study is the fact that all of the cells utilized, both normal and malignantly transformed, were derived from an original cloned cell.