Technical Abstract: Chickens were intranasally inoculated with Chilean H7N3 avian influenza (AI) viruses of low pathogenicity (LP), high pathogenicity (HP) and a laboratory derivative (02-AI-15-#9) from the LPAI virus to determine pathobiological effects. One LPAI virus inoculated chicken exhibited mild depression and developed antibodies against AI virus. None of the chickens inoculated with the laboratory derivative exhibited clinical signs or died and only one had serological evidence of infection. All chickens inoculated with HPAI virus became infected and died on 2 or 3 days post inoculation (DPI) with a few showing moderate depression before death. The HPAI virus produced focal hemorrhages of the comb, petechial hemorrhage at the esophageal-proventricular junction and proventricular mucosa, edema and congestion of the lung, petechiation of the spleen, and generalized decrease in body fat. Histologically, severe necrosis, hemorrhage, and/or inflammation were primarily identified in lungs and the lymphoid tissues. All tissues sampled from the HPAI group were positive for the AI viral antigen, predominantly in endothelium of blood vessels throughout most tissues, and less frequently in histiocytes and cellular debris of lymphoid tissues. Even less consistently, cardiac myocytes, hepatocytes, Kupffer¿s cells, glandular epithelial cells, microglial cells and neurons became infected. These studies suggest the Chilean LPAI virus was poorly infectious for chickens and may have been recently introduced from a non-galliforme host. By contrast, the HPAI virus was highly infectious and lethal for chickens. The HPAI virus had a strong tropism for the cardiovascular system, principally vascular endothelial cell that is a similar viral tropism as demonstrated with some previously examined H5 and H7 HPAI viruses.