Idiotypic profiles of autoreactive monoclonal antibodies (MoAb) were evaluated by their reactivity with a panel of alkaline phosphatase (AP)-coupled detector MoAb derived from the same fusions. Attention was given to the question of whether differences exist between MoAb derived from spleen cells (SC) or thymocytes (TC) and whether ID profiles would change during post-natal development. In the newborn, natural autoantibodies and MoAb which did not react with any one of eight autoantigens displayed different ID profiles, autoreactive MoAb being characterized by the expression of a restricted pattern of ID. During post-natal development, changes of ID expression were only observed with autoreactive MoAb. Many ID which were detected on MoAb derived from 6-day-old mice were not detected on SC-derived MoAb from young adults, while a few ID were significantly over-represented. Furthermore, especially with TC-derived MoAb, a clear linkage between certain idiotypes and autoantigen specificities could be demonstrated. Thus, in contrast to non-autoreactive MoAb, natural autoantibodies in the young adult were characterized by expressing only a selected number of ID at high frequency. Furthermore, the B-cell environment apparently played a role, since there were marked differences between ID profiles of TC- versus SC-derived MoAb. The data are interpreted in the sense that expansion and maturation of naturally activated autoreactive B cells are controlled rather than being random processes.