In the anuran Xenopus, as has been demonstrated previously in several species of urodele Amphibia, histone genes lie at the sphere organizer loci of the lampbrush chromosomes. They were located by in situ hybridization of a 3H-labelled histone H4 anti-sense cRNA probe applied to lampbrush preparations in which transcript RNA had been retained, and likewise to preparations in which transcripts were absent but whose DNA had been denatured prior to hybridization. In Xenopus the histone genes lie in intimate association with the spheres that are attached to the lampbrush chromosomes, but they are absent from spheres that lie free in the germinal vesicle. The Anura separated from the Urodela several hundred million years ago, so the sphere organizer/histone gene association is of great antiquity. This suggests that the association has a functional significance, though it is one that has yet to be discovered.