Very few cultured CD8+ T cell clones can normally be obtained from a single mouse and maintained in long-term culture. To improve the yield, we immunized p53 mutant mice with peptides of Sendai virus (FAPGNYPAL) and influenza virus (ASNENMETM) origin. Substantially more clones could be derived from p53-/- mice than from similarly treated wild-type mice (p53+/+); an intermediate yield was obtained from heterozygous mice (p53+/-). CTL lines or clones from p53-/- mice exhibited greater proliferative activity and resistance to gamma-irradiation than those from p53+/+ mice, and were cytolytically potent.