BALB/c and CBA/CaH mice show discrete, genetically determined patterns of tissue responses to infection with the yeast Candida albicans. By use of a semiquantitative reverse transcriptase-polymerase chain reaction, interferon (IFN)-gamma, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha were readily demonstrated in brain tissue on days 1, 3, and 5 after infection and were present in higher concentrations in CBA/CaH than in BALB/c mice. IL-2 and -4 were detected in both strains but at different time points. Both the fungus burden and the severity of the tissue damage become established before mRNA concentrations of the cytokines increase in the lesions, and the rate of clearance of the yeast is similar in both mouse strains. The data indicate that the deterministic model, which correlates Th1 and Th2 cytokines with resistance and susceptibility, respectively, is inadequate to account for the patterns of cytokine production that develop in the infected brain after sublethal challenge.