The immunogenicity of Gross virus cell surface antigen (GCSAa) extracted from rat lymphoma cells can be dramatically increased by its presentation into liposomes, probably by mimicking the cell membrane presentation. Induction of an anti-GCSAa secondary antibody response has been found to require the use of liposomes as GCSAa vehicle for both the priming and the boosting immunizations. In order to investigate the sensitivity of highly immune cells to the liposome presentation, immune spleen cells were stimulated in vitro with either soluble GCSAa or GCSAa-liposomes and transferred together with the immunogen into syngeneic animals. Only spleen cells from high responders, which have been immunized twice with GCSAa-liposomes, were able to generate an antibody response in naive recipients after their restimulation with the GCSAa-liposome preparation. Their restimulation with soluble antigen was ineffective unless 10% peritoneal exudate cells (PEC) from naive rats were added during the in vitro incubation. Stimulation with GCSAa-liposomes was further improved by the addition of 10% PEC. Macrophages were found to play a central role in the induction of antibody response in the recipients after stimulation with GCSAa-liposomes. Treatment of immune spleen cells with the macrophage-killing agent leucine methyl ester prior their restimulation in vitro with GCSA-liposomes in the absence of PEC, or depletion of macrophage after their in vitro incubation with this immunogen, completely abolished the induction of anti-GCSAa antibodies in the recipients.