When, under the influence of inactivated Sendai virus, the nucleus of a mature hen erythrocyte is introduced into the cytoplasm of a human or mouse tissue culture cell, it resumes the synthesis of RNA and DNA. This reactivation of the red cell nucleus in the heterokaryon is associated with a marked increase in its volume. There is a direct relation between the volume of the nucleus and the amount of RNA that it makes. The nuclear enlargement is not the consequence of increased RNA synthesis, or of DNA synthesis: enlargement is the primary event, and the increase in RNA synthesis is determined by it. During the process of reactivation, the erythrocyte nucleus shows a five- to six-fold increase in dry mass which takes place largely before the replication of DNA begins. This increase is due to the passage of cytoplasmic proteins into the erythrocyte nucleus. The physical properties of the deoxyribonucleoprotein complex in the erythrocyte nucleus change as the nucleus enlarges. The ability of the nuclear chromatin to bind acridine orange and other intercalating dyes increases four- to fivefold; and changes in the melting profile of the deoxyribonucleoprotein indicate that its structure is loosened. It appears that, as the nucleus expands, more of the chromatin passes from a condensed to a dispersed state and more of it is transcribed. At the concentrations used to induce cell fusion, Sendai virus is haemolytic and rapidly lyses the nucleated erythrocytes. Fusion then takes place between the other cells in the combination and erythrocyte ghosts. The erythrocyte nucleus is thus introduced into the cytoplasm of the recipient cell without any appreciable contribution of erythrocyte cytoplasm. The reactivation of the hen erythrocyte nucleus is therefore achieved by signals emanating from human or mouse cytoplasm.