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Pythium aphanidermatum is a common plant pathogen, reportedly capable of human infection. This study investigated whether P. aphanidermatum can infect domestic rabbits. Four rabbits were inoculated with P. aphanidermatum subcutaneously and evaluated for 30 days. Blood and tissue samples were collected from all animals. The animals developed palpable nodules 5-10 days after inoculation. Necropsy revealed caseous nodular lesions characterized histopathologically by pyogranulomatous inflammation containing hyphae in the necrotic areas. P. aphanidermatum was isolated from the caseous material and anti-P. aphanidermatum antibodies were detected by serological examination. This is the first report of experimental P. aphanidermatum infection in mammals. The results demonstrate that this oomycete can produce infection at the inoculation site and induce an immune response. The results suggest that P. aphanidermatum may be undergoing adaptation to vertebrate hosts., (Copyright © 2021 Elsevier Ltd. All rights reserved.)