Viruses that cause in vivo persistent infections avoid the host's immunologic surveillance machinery. A major component of that armamentarium is virus-specific MHC-restricted cytotoxic T lymphocyte (CTL) response of the host. Studies with lymphocytic choriomeningitis virus (LCMV) have uncovered a parental virus (CTL+) that in immuno-competent adults induces CTL and terminates acute infection and a variant (CTL-) that fails to elicit CTL responses and establishes a persistent state (R. Ahmed et al. (1984) J. Exp. Med. 160, 521-540). The biologic properties, similarities, and differences between CTL+ and CTL- viruses as regards their interactions with lymphocytes of newborn and adult mice is recorded here. CTL+ and CTL- viruses persist in lymphocytes of newborn inoculated mice, primarily within the T helper subset. Approximately 2% of lymphocytes express viral nucleic acid sequences while only 0.04% score as infectious centers suggesting incomplete viral replication. These levels were maintained over the course of infectious. In contrast, CTL- virus but not CTL+ persists in lymphocytes of mice inoculated when adults. Lymphocytes easily scored as infecting centers but rarely displayed nucleic acid sequences suggesting a different balance of incomplete to complete virion replication. Further, infectious centers decreased by 10-fold from the 3rd to 68th day of infection and the total numbers of T lymphocytes in the circulation decreased suggesting CTL- may replicate in and destroy lymphocytes of adult mice. In the following paper the primary nucleotide structure of the LCMV small RNA segment, the segment responsible for generation of CTL and encoding the proteins recognized by CTL, for CTL+ and CTL- viruses is reported.