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We studied in vitro immune response to fleas in two gerbils, Gerbillus dasyurus and Gerbillus andersoni allenbyi, which differed in their natural species richness of flea assemblages and prevalence of infestation. G. dasyurus is parasitized naturally by several flea species, but the prevalence of infestation is low, whereas G. a. allenbyi is parasitized by a single flea species, with high prevalence of infestation. We hypothesized that immunological parameters and the cell-mediated specific immune response to an antigen from an unfamiliar flea species differ between the two gerbil species. Parasitized and control gerbils of both species demonstrated similar, relatively low levels of spontaneous glucose consumption. The same was true for the phytohemagglutinin treatment. Responses to antigen from unfamiliar flea species were higher than both spontaneous glucose consumption and response to phytohemagglutinin in parasitized and control G. a. allenbyi and parasitized G. dasyurus. However, no significant difference in the spontaneous blast transformation index and responses to both phytohemagglutinin and flea antigen was found in control G. dasyurus. The number of white blood cells was significantly lower in control than in parasitized G. dasyurus, whereas no difference in the number of white blood cells was found between control and parasitized G. a. allenbyi. The levels of circulating immune complexes and concentrations of immunoglobulins did not differ between parasitized and control individuals in both species. Phagocytic activity was significantly higher in males than in females of G. a. allenbyi but not of G. dasyurus. In addition, phagocytes of G. dasyurus appeared to be significantly more active than those of G. a. allenbyi.