The sera of patients with rheumatoid arthritis form a precipitate with an antigen present in the sonicate of a human B (bone marrow-derived) lymphoid cell line (WiL2). The antibody is distinct from rheumatoid factor. The antigen can be demonstrated by an immunofluorescence technique to be distributed within the nucleus of the WiL2 cell and shows a discrete speckled pattern of nuclear staining. The nuclear antigen is not detectable in organ extracts from many animal species or in human T (thymus-derived) lymphoid cell lines. The current evidence suggests that the nuclear antigen is detectable only in human B lymphoid cells infected with Epstein-Barr virus. It is not clear at present whether the nuclear antigen is a viral protein or a cell protein induced by the Epstein-Barr virus as a result of polyclonal B cell activation.