Genetic or DNA-based immunization, including genomic immunization, has shown to be a viable alternative approach to induce protective immunity against a number of pathogens in several disease models. Here we describe a new method, cDNA expression library immunization (cDELI), based on the use of a large number of cDNA clones. This immunization strategy was tested in experimental murine Taenia crassiceps cysticercosis model. A partial cDNA expression library of 2 x 10(4) members was constructed in eukaryotic expression vector pcDNA3 and used to immunize BALB/c female mice subcutaneously (s.c.) and intramuscularly (i.m.). In both cases significant reduction of parasite load (up to 65%) was obtained. We were unable to directly measure T. crassiceps-specific humoral immune response in any of the immunized mice, although the expression of pathogen proteins in vitro in macrophages transfected with cDNA expressing plasmids was demonstrated. Also, in three out of five randomly selected immunized mice detectable levels of interferon-gamma (IFN-gamma) were obtained. cDELI has additional advantages compared with recently developed single gene or genomic immunization approaches because a cDNA population represents only those genes that are being expressed in the pathogen cells and the selection of stage-specific antigens is possible. The use of cDELI could be particularly attractive for the pathogens with complicated life cycles and large genomes.