Larvae of Galleria mellonella are useful models for studying the virulence of microbial pathogens or for evaluating the potency of antimicrobial agents. In this work we demonstrated that prior exposure of larvae to non-lethal doses of Aspergillus fumigatus conidia increases the resistance of larvae to a lethal dose (1 x 107 20 μl-1) 24 h later. Exposure of larvae to a conidia concentration of 1 x 104 20 μl-1 leads to an increase in hemocyte density but an inoculum of 1 x 105 conidia leads to enhanced expression of antimicrobial peptides, increased binding of proteins (e.g., arylophorin, prophenoloxidase, apolipophorin) to conidia and elevated hemocyte density. These results suggest that a low dose of conidia (1 x 104) predominantly activates the cellular immune response but that a higher dose (1 x 105) that is still not lethal activates a humoral immune response to the greatest extent. While insects have an immune system analogous to the innate immune response of mammals these results suggest that it is capable of assessing the extent of the microbial challenge and mounting a ‘proportionate’ immune response which may have important survival advantages.