The mechanisms underlying resistance to re-infection with lymphocytic choriomeningitis virus (LCMV) were investigated. Rechallenge with moderate doses of virus (10(3) LD50) did not lead to detectable re-infection nor to re-induction of virus-specific cytotoxicity. When higher doses of virus were used for rechallenge (10(6) - 10(8) LD50), significant re-infection as well as reactivation of cytotoxicity were observed. Both resistance and memory expression were controlled by an antigen-specific, radio-resistant factor in the immune mouse. Transfusion of serum from immune mice to naive recipients markedly reduced both virus take and the LCMV-specific immune response. In contrast, transfer of primed cells did not have an immediate effect on virus titres in naive recipients; instead an enhanced immune response was detected and accelerated virus clearance was the result. Based on these observations we conclude that preformed antibodies constitute a primary barrier to re-infection with LCMV; only if the first line of defence fails, does memory function become critical and a secondary immune response induced. In the latter case the accelerated kinetics of this response will ensure that the infection is controlled before substantial cell damage has occurred. We find no need to invoke active suppression of immunity in order to explain the difficulty to obtain a typical memory response in situ.