The development of IgG L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT)-specific plaque-forming cell responses in vitro by virgin and immune (responder × nonresponder)F1 spleen cells after stimulation with responder and nonresponder parental GAT-macrophages (Mπ) was investigated. Virgin F1 spleen cells developed comparable primary responses to both parental GAT-Mπ. By contrast, F1 spleen cells from mice immunized with GAT or responder parental GAT-M developed secondary responses after stimulation with only responder parental GAT-Mπ Spleen cells from F1 mice immunized with nonresponder parental GAT-Mπ developed secondary responses to these GAT-Mb, but failed to respond to respender parental GAT-Mπ These results are discussed in the context of genetic restrictions regulating Mπ-T-cell interactions in secondary antibody responses and the possible expression of Ir-gene function in Mπ. © American Society for Clinical Pathology.