Attempts to reproduce swollen head syndrome (SHS) lesions were carried out in specific pathogen-free (SPF) chickens. In Experiment 1, chickens inoculated into the submucosal tissue of the nasal membrane or subcutaneous tissue of eyelids with four different strains of Escherichia coli, developed typical SHS lesions; purulent and necrotic lesions of facial subcutis (especially around their eyelids), periocular connective tissue, infraorbital sinus, air spaces, middle ears and eyeballs. The lesions elsewhere included splenic necrosis with fibrinous exudation, fibrin thrombi in hepatic sinusoids, and fibrinopurulent epicarditis and perihepatitis which occasionally accompanied lesions in SHS cases. In Experiment 2, SPF chickens inoculated intranasally with turkey rhinotracheitis (TRT) virus and/or E. coli showed no significant lesions in the facial skin, upper respiratory tract or other organs. However, the presence of TRT antibodies demonstrated that the virus infected the chickens. This study suggests that E. coli may play a significant role in the pathogenesis of SHS, but that the significance of TRT virus in the pathogenesis is still to be clarified.