Human epidermoid carcinoma (HEp-2) cells infected with Herpes simplex virus formed syncytia which, occasionally, contained nuclei in prophase or mitotic figures resembling chromosomes at metaphase. Syncytia of cultures treated with colchicine did not show a marked increase in the proportion of mitotic figures despite the accumulation in the culture of large numbers of cells arrested in metaphase. Withdrawal of the colchicine from the infected cultures resulted in the formation of macrokaryocytes consisting of a thin rim of cytoplasm and a macrokaryon containing mitotic figures, dispersed chromosomes, and other substances with staining properties of nuclear material. It was concluded that anaphase or telophase are not blocked by virus and that cells are susceptible to recruitment into syncytia in interphase and prophase. Since the resistance to recruitment into giant cells of nuclei arrested in metaphase by colchicine could be reversed by withdrawing the drug without reversal of the inhibition of spindle formation, it was concluded that these two phenomena are functionally independent. Fluorescein antibody staining of syncytia containing nuclei in interphase revealed the early appearance of virus antigen at the nuclear membrane and subsequent accumulation of the antigen in the cytoplasm. In the macrokaryocytes virus antigen was localized around some, but not all, of the mitotic figures inside the macrokaryon. These observations support the view that virus antigen synthesis takes place in structures associated with the nucleus, possibly just before, or at the time that, incomplete virus particles migrate from the nucleus into the cytoplasm.