The pathogenicity of lymphocytic choriomeningitis virus (LCMV) inoculated intracerebrally (i.c.) varies with virus strain and dose as well as with the mouse strain used as host. Recently, results have indicated that susceptibility to lethal disease correlates directly the ability of the host to produce early and high virus-specific Tc activity. However, in the present studies we demonstrate that even though this holds true in many mouse/virus combinations, it does not apply in others. Thus, in C3H mice infected with (moderately) high doses of Traub strain LCMV, early and high Tc activity was found despite a mortality rate of only 10-20%. Similarly, in C3H mice inoculated with the aggressive and docile substrains of UBC strain LCMV, which differ markedly in their pathogenicity for this mouse strain, similar kinetics of Tc induction were observed. Finally, in DBA/2 mice which do not die following infection with the otherwise lethal aggressive substrain, Tc induction could be found to be as efficient as in BALB/c mice, all of which die from acute LCM disease when infected with this virus isolate. The results indicate, therefore, that early and high Tc activity does not constitute a sufficient prerequisite for lethal disease, and that different Tc response profiles may be associated with low mortality following i.c. inoculation with LCMV.