The activation of the mouse embryo genome has been studied during early cleavage, in vivo. Individual embryos, prepared as whole mounts, were assayed for endogenous RNA polymerase activity. RNA synthesis was detected by autoradiography as the incorporation of [3H]UMP into an acid-insoluble product. No RNA polymerase activity could be detected in the pronuclei of one-cell embryos. Radioactive incorporation was first evident in the nuclei of two-cell embryos. This appeared to be confined to the nucleoplasm and could be abolished by alpha-amanitin but not by low concentrations of actinomycin D. Polymerase activity which was not affected by alpha-amanitin was first detected in the four-cell embryo, predominantly at the peripheries of the nucleoli. Nucleolar labelling increased markedly between subsequent cleavages, reaching a peak in early morulae. In one- and two-cell embryos, label incorporation could be found in the nucleus of the persisting polar body.