Indirect immunofluorescence has been used to detect the presence of histone H5 in single cells during avian erythropoiesis. Evidence is presented which demonstrates that this method specifically detects histone H5. The results show that the increase in the amount of H5 which can be extracted from nuclei during erythropoiesis is accounted for both by an increase in the amount of H5 per cell and by an increase in the total number of cells containing histone H5. Of particular interest are the observations that histone H5 is arranged within the nucleus in several distinct, reproducible patterns and that different patterns predominate at different stages of erythroid cell development. In addition to suggesting new possibilities for the role of histone H5, these findings indicate that immunofluorescence may be used profitably to explore the supramolecular organization of chromatin.