Mice were primed with TNP-derivatized insulin, or TNP-Mycobacteria, and lymph node cells were challenged in vitro with haptenated and unhaptenated antigens. Using either priming antigen, T-cell proliferative responses could be obtained to TNP-insulin. In B10 (H-2b), mice, which are responders to beef insulin (BI), but not to pork insulin (PI), TNP-BI or TNP-PI primed a response to TNP beef and TNP pork insulins, and to beef but not pork insulin, suggesting that a proportion of the response was directed to the modified portion of the molecule. However, priming with BI resulted in responsiveness to TNP-PI, but not to PI. Also, TNP-BI stimulated an augmented proliferative response in BI-primed mice. These results suggest that TNP modification can alter the antigenicity of the carrier molecule, perhaps by enhancing weak interactions with MHC molecules on presenting cells. Finally, there was no evidence that the TNP-dependent response to TNP-pork insulin was down-regulated by suppressor cells directed at the carrier molecule.