Studies from this laboratory have indicated that isologous myeloma protein 315 (M315, isotype IgA, lambda 2) elicits T helper cells which recognize processed forms (peptides) of its V-domains and that recognition is controlled by H-2 linked immune-response (Ir) genes (J Exp Med 1982; 155:1587-96; Eur J Immunol 1986; 16:889-93). We now report that adjuvant-free soluble M315, particularly the mildly reduced and alkylated form, stimulates a T-dependent antibody response mainly specific for M315's paired V-domains. A small subset of the antibodies appeared to recognize the C-region of IgA, thus being analogous to rheumatoid factors (RF). On the basis of these observations, we propose that one pathway to RF production depends on T helper cells that interact directly with RF-producing B cells across peptide-MHC bridges. These peptides are envisaged to be derived from hypervariable regions of IgG V-domains, and they are therefore called "idiotypic peptides". This hypothesis assumes that the number of different idiotypic peptides is so large that the immune system has not developed tolerance to all of them.