Memory is a hallmark of the immune system and ever since its recognition there has been considerable interest in understanding how immunity is maintained(1-5). The current model is that long-term memory is dependent on persistent antigenic stimulation(6-11). We report here results that challenge this view and provide evidence that antigen is not essential for the maintenance of CD8(+) T-cell memory. We show that memory CD8(+) cytotoxic T lymphocytes persist indefinitely in the absence of priming antigen, retain the memory phenotype (CD44(hi)), and provide protection against virus challenge. These findings suggest a re-evaluation of our current thinking on mechanisms involved in maintaining immunity and have implications towards designing effective vaccination strategies.