Cytokine mRNA levels were assessed in Burkholderia pseudomallei-susceptible BALB/c mice and B. pseudomallei-resistant C57BL/6 mice following administration of a sublethal dose of less virulent (LV) B. pseudomallei, a candidate immunogen tested for protection against a highly virulent (HV) challenge. Compared on the basis of the bacterial loads, the cytokine patterns induced by HV and LV B. pseudomallei were similar, involving gamma interferon, interleukin-10, and other cytokines. Partial cross-protection between B. pseudomallei strains is shown to be associated with cytokine profiles involving both type 1 and type 2 cytokines.