. Antibodies to a set of structurally related autoantigens (p23-25) bind to a previously uncharacterized, large structural domain in the nucleus of a variety of human cell types. This subnuclear domain is visible by phase contrast alone as a region of decreased density after several different fixation protocols . The morphology of this region changes dramatically during the cell cycle and we have given it the name PIKA (for polymorphic interphase karyosomal association) based on preliminary evidence that the PIKA proteins may be associated with chromatin . The function of the PIKA is not yet known, but our immunolocalization B EYOND such obvious features as the nucleolus, heterochromatin, and the nuclear membrane, the structural organization of the nucleus is surprisingly poorly understood . While many aspects of nuclear physiology have proven amenable to analysis in vitro, a complete understanding of the cellular control of nuclear processes, which include transcription, nascent RNA splicing and processing, and transport of mature mRNA, may ultimately depend on our knowledge of the organization of the nucleoplasmic material surrounding the interphase chromosomes. At present, much about the organization ofthe nucleoplasm remains unclear. Specifically, it is unknown to what extent the nucleoplasm is functionally and structurally partitioned into separate domains .Efforts to understand the structure of the nucleoplasm by biochemical fractionation have met with only limited success. Many attempts at separating the nucleus into its constituent substructures have involved disruptive procedures such as nuclease digestion and/or detergent and salt extraction (Berezney and Coffey, 1975;Berezney, 1984;Vogelstein et al ., 1985) . Biochemical fractionation procedures have permitted identification of proteins associated with small nuclear RNA (snRNA) ' (Lerner and Steitz, 1979; Pettersson W . S. Saundees present address