We investigated at the ultrastructural level, by different cytochemical and immunocytological approaches, the behavior of interchromatin granules (IGs) during interphase and mitosis in two cell lines (HEp-2 and Ehrlich tumor cells). Identical results were found in all two cell types. In interphase cells, IGs group into irregular clusters of varying size. They are frequently associated with coiled bodies and homogeneous fibrillar bodies. Analysis of serial sections reveals that IG clusters occupy distinct regions within the nucleoplasm. During prophase, the aggregation of granules in these clusters gives rise to compact, spherical, granular structures. These disperse in the mitotic cytoplasm at the breakdown of the nuclear envelope. At early telophase, some of them come into close contact with the periphery of reforming nuclei. IG clusters reappear in the daughter nuclei only after the chromosomes have decondensed during late telophase. Concomitantly, the cytoplasmic granular structures disappear. During the cell cycle, IG are silver-stainable and EDTA-positive. They are also constantly labeled by the polyadenylate nucleotidyl transferase-immunogold technique for detecting RNA. These results support the view that IGs persist throughout the whole cell cycle.