A new method for the cytological analysis of antinuclear antibody binding offers several advantages over conventional techniques. Nuclei in meiosis, prepared by surface-spreading spermatocytes, provide a detailed examination of the constituents of the nucleus--euchromatin, heterochromatin, sex chromatin, nucleoli, centromeres, and dense patches that seem related to RNA metabolism--and each of these structures can be seen to change in morphology and antibody labeling during the course of meiotic prophase. Results using sera from humans and mice with autoimmune disease, and using several mouse monoclonal antibodies, demonstrate the potential of this method for clinical and research applications, both for more common antibody types and for those that bind epitopes which are unique to germ cells.