Mice were injected with TNP-KLH in one front footpad and challenged in both front footpads 1 to 16 wk thereafter. The response of the contralateral node was significantly lower than that of the ipsilateral node early and again late, but not at intermediate, intervals after priming. This difference was not abolished by boosting with a higher dose of antigen or by administering excess carrier-primed helper T cells before challenge with antigen. The ipsilateral brachial lymph node cells transferred significantly higher B cell memory responsiveness at all intervals after priming than the contralateral lymph node, although at 2 to 4 wk both lymph nodes transferred substantial memory. At later intervals (more than 8 wk) only the ipsilateral lymph nodes transferred significant memory for TNP. Priming in the front footpads did not result in a splenic primary response, but a secondary response was observed in the spleen after boosting in the footpads. The relative importance of antigen localization and circulating memory cells in determining induction and persistence of memory in sites of lymphoid tissue proximal and distal to antigen injection is discussed.