ABSTRACT Unlike most embryonic cells, myoblasts do not normally divide when they undergo differentiation to form ‘muscle straps’ and subsequently muscle fibres. Their nuclei retain their individuality, and consequently this material is particularly suitable for studying the fate of nucleolar material during a process of cell differentiation. Measurements were therefore made with an interference microscope on the nucleoli of living chick myoblasts in tissue culture preparations ; and values for their volume, dry mass, and % solid content were obtained at three distinct stages of the differentiation process, the uninucleate stage, the binucleate stage, and the multinucleate stage. It was found that the nucleoli of binucleate myoblasts had, on the average, less than half the dry mass and less than half the volume of the nucleoli of the uninucleate cells. The changes in the volumes of the nucleoli were especially striking, and it was subsequently demonstrated, by means of sequences of photomicrographs of myoblasts in developing cultures, that, during the process of association and probable fusion of two uninucleate myoblasts to form a binucleate cell, one or more of the nucleoli can be observed to shrink visibly in their linear dimensions. As an explanation of these results it is suggested that, during the process of differentiation and tissue building characterized by the association and apparent fusion of two myoblasts, relatively large amounts of RNA or RNP may pass from the nucleoli into the cytoplasm so that the nucleolar material becomes temporarily depleted ; and that subsequently, after the cells have joined, this regains its former level. Some support for this suggestion was provided by the finding that the mean values for the dry mass and volume of the nucleoli in the multinucleate myoblasts were intermediate between those of the uninucleate and binucleate myoblasts, because the multinucleate cells are the product of both recent and less recent fusions of cells.