An oomycotic pathogen in the genus Lagenidium was isolated from tissues obtained from 6 dogs with progressive cutaneous disease. Initial clinical findings in 5 dogs included multifocal cutaneous lesions, subcutaneous lesions, or both associated with regional lymphadenopathy: the 6th dog initially was presented for evaluation of mandibular lymphadenopathy. Cutaneous lesions were ulcerated, exudative regions (often with necrosis and draining tracts) or multiple firm dermal or subcutaneous nodules. Two dogs subsequently developed hemoabdomen from great vessel rupture and died acutely. Four dogs were euthanized because of progression of subcutaneous lesions or lymphadenopathy. On postmortem examination, regional granulomatous lymphadenitis was found in all 6 dogs, great vessel invasion in 3 dogs, pulmonary lesions in 2 dogs. ureteral obstruction in 1 dog, mediastinal lymphadenitis in 1 dog, and hilar lymphadenitis with invasion of the distal esophagus and trachea in 1 dog. Histologically, lesions were similar to those associated with pythiosis and zygomycosis and were characterized by severe eosinophilic granulomatous inflammation (often with numerous large multinucleated giant cells) centered around broad (7-25 micro), infrequently septate hyphae. Immunoblot analysis of the serologic response of 4 dogs to a soluble mycelial extract of Lagenidium giganteum indicated that each dog's serum recognized at least 10 different antigens of L. giganteum. Culture of infected tissues yielded rapid growth of colorless to white submerged colonies. Microscopically, mature hyphae in culture were broad (25-40 micro), segmented, and occasionally branching and produced motile laterally biflagellate zoospores in water culture. This report is the 1st description of infection caused by an oomycete other than Pythium insidiosum in any mammalian species.