Inoculation of A/J mice with the small monovalent compound L-tyrosine-p-azophenyltrimethylammonium, tyr(TMA) induces antigen-specific T cell helper activity. This was assessed as follows: mice were inoculated with either 100 μg of tyr(TMA), L-tyrosine-p-azobenzenearsonate, tyr(ABA), or complete Freund's adjuvant (CFA) alone, followed 1 wk later with TMA-bovine serum albumin (BSA), or TMA-human γ-globulin (HGG). Ten days later the animals were boosted with either TMA-BSA or TMA-HGG and the plaque-forming cells (PFC) to TMA were enumerated. Mice revealing tyr(TMA) showed a 4-fold enhancement in PFC over that of tyr(ABA) or CFA-primed animals. This enhancement in tyr(TMA)-primed mice is antigen specific at the efferent limb since substitution of TMA-BSA or TMA-HGG with dinitrophenol coupled to BSA (DNP-BSA)did not result in an augmented response to DNP. Enhancement was apparently due to helper T cell activity since helper activity could be transferred into lethally irradiated mice by nylon wool-purified T cells but not by anti-T cell treated, tyr(TMA)-primed spleen cells. These data indicate that tyr(TMA) determinants on the BSA molecule mediate cooperation between T and B cells in a 'self-help' fashion, to generate anti-TMA PFC. Further experiments were carried out to determine if anti-idiotypic antiserum (anti-Id) directed to anti-TMA antibody could prime tyr(TMA) helper T cells. To this end, A/J mice were primed with either anti-Id or normal rabbit serum (NRS) in lieu of tyr(TMA) or CFA alone and then inoculated with TMA-BSA. The anti-Id primed group showed a 4-fold increase in anti-TMA PFC over the NRS-primed control population. Helper activity could not be induced after passage of the anti-Id over anti-TMA antibodies bearing the cross-reactive idiotype(s) (CRI-TMA) bound to Sepharose 4B. Anti-Id induced enhancement was apparently due to helper T cell activity since this activity could be transferred into lethally irradiated mice by T but not B cells. In addition, tyr(TMA)-induced T helper activity could be blocked by anti-Id at the efferent limb before transfer into irradiated recipients. These results suggest that T helper cells bear cross-idiotype(s) and that anti-Id induces CRI+ helper activity rather than eliminates CRI+ TMA-specific suppressor cells. Finally, anti-Id induced TMA-specific helper activity in the CRI+ C57.Ige strain (H-2b,Ige) that shares the same allotype as the A/J strain, but not in its congenic partner C57BL/6 (H-2b Ig-1b). The significance and interpretation of these results are discussed.