MyD88, a protein implicated in interleukin-1 signaling, was localized in HeLa cells transiently transfected with an epitope-tagged (flag) version of MyD88. Overexpression of MyD88 can induce apoptosis. We have analyzed the fine structural intracellular distribution of MyD88 using immunoelectron microscopy. MyD88 is localized to the nucleus and to the cytoplasm as revealed by immunofluorescence visualization. Ultrastructural immunocytochemistry shows that, in the cytoplasm, this protein is associated with fibrillar aggregates containing beta-actin. In the nucleus, MyD88 was found in fibrillar domains present only in cells not yet displaying morphological signs of apoptosis. These domains are not derived from nucleoli and do not constitute an accumulation site of splicing factors. We suggest that such structures could be involved in the formation of the apoptotic bodies and/or in the modification of the nuclear structure and of nucleocytoplasmic trafficking during apoptosis.