Antigen stimulated cultures of rabbit and human peripheral blood lymphocytes (PBL) were maintained in active antibody synthesis for at least a month. When rabbit PBL were used, the response to a particulate antigen (SRC) was not affected by a change of medium and/or by disruption of the cell to cell contact during culture. On the other hand, the response to a soluble antigen (OA) was markedly increased by changing the medium after the onset of the response. When human PBL were used, any handling that caused disruption of cellular contacts was detrimental for continuation of the specific response. In both the rabbit and the human system the overall cell number did not increase during culture, but an enrichment in the specific cells occurred. These cultures represent a powerful tool both for studies of late events of the immune response and for the aim of establishing antibody producing cell lines.