Experiments with somatic cell hybrids and stable heterokaryons have demonstrated that differentiated cells exhibit a remarkable capacity to change. Heterokaryons have been particularly useful in determining the extent to which the differentiated state of a cell is plastic. Cell fate can be altered by a change in the balance of positive and negative trans-acting regulators. Although a single regulator may be sufficient in certain environments to trigger a change in cell fate, that regulator may be ineffective in other cell contexts where it encounters a different composition of regulators.