Plasmid DNA expressing the major outer membrane protein (MOMP) of an avian Chlamydia psittaci serovar A strain, has been tested for its ability to raise an immune response and induce protection against challenge with the same serovar. A combined parenteral (intramuscular injection) and mucosal route (DNA drops administered to the nares) of DNA inoculation was compared to gene gun-based immunization. The gene gun delivery of pcDNA1/MOMP as well as the intramuscular-intranasal DNA delivery primed both T-helper and B-cell memory although rMOMP-expressing cells did not induce high antibody responses. Evidence for the priming of the memory was provided by the fact that the pcDNA1/MOMP inoculations raised antibodies belonging to the IgG and not IgM isotype. However, in response to challenge only 5 out of 15 vaccinated turkeys showed four fold increases in serum IgG after challenge. By contrast, evidence for the priming of T-cell memory in response to challenge was found in all vaccinated turkeys as shown by the significantly heightened proliferative responses of peripheral blood lymphocytes following vaccination. Both immunization methods produced similar serological and lymphocyte proliferative responses. Notwithstanding the immunization method, a significant level of protection was observed in all pcDNA1/MOMP immunized turkeys. The efficacy of MOMP-based DNA vaccination as a means of preventing severe clinical signs, lesions and chlamydia excretion in a turkey model of Chlamydia psittaci infection was demonstrated.