A large number of hybridomas were constructed by fusion of B cells from perinatal liver and spleen. Many of these showed multispecificity, high interconnectivity and anti-idiotype (Id) activity. Several of these were subjected to a detailed analysis to evaluate their influence on the developing immune system. A hybridoma BD2 (mu,kappa), derived from 2-day-old liver, was shown to have anti-T15 and anti-J558 activity by inhibition enzyme-linked immunosorbent assay and by in vivo administration. BD2 reduced primary T15 and J558 Id in adult BALB/c by 50%. In contrast, timed administration of this antibody during neonatal periods resulted in enhancement of responses to phosphorylcholine (PC) and alpha (1----3)-linked dextran (Dex) when these mice were challenged as adults. Another hybridoma DB3 (mu,kappa), derived from a lipopolysaccharide-stimulated fetal liver, reacts with GB4-10 (anti-T15) and not with PC. It also reacts with BD2. It is thus anti-anti-Id with respect to T15 and J558. Early administration of this antibody also led to an enhancement of anti-PC and anti-Dex responses, apparently via expansion of a set of intermediate anti-Id BD2-like B cells. In adult mice it suppressed responses to both antigens. A third hybridoma FC4 (mu,kappa), derived from 3-day-old spleen, reacts with GB4-10 as well as EB3-7 (anti-J558). Introduction of this antibody into neonatal mice enhanced anti-Dex responses while in adults it caused suppression of T15 Id. The results presented here suggest a possible role for neonatal anti-Id B cells in the primary activation of antigen-reactive B cells by Id selection.