Objective - To experimentally infect adult alpacas by ID inoculation of Corynebacterium pseudotuberculosis, follow the clinical and pathologic course of disease, and study the humoral response to infection. Animals - 13 adult alpacas. Procedures - 9 alpacas were inoculated with 1.1 × 106 CFUs of C pseudotuberculosis from llama (n = 4) or alpaca (5) origin, and 4 alpacas were sham inoculated as controls. Alpacas were clinically observed after inoculation and euthanatized on days 16, 58, 93, or 128 after inoculation; necropsy examination and histologic evaluation were performed. An indirect ELISA, which made use of the C pseudotuberculosis cell wall as the antigen, was used to measure antibody titers in serum samples. Results - Alpacas had a persistent febrile response, a local severe inflammatory response, and leucocytosis (> 30 × 103 WBCs/μL). Internal abscesses that localized mainly in the renal lymph node were observed. Corynebacterium pseudotuberculosis was recovered from the inoculation site 1 week after inoculation and from internal abscesses at 58 days after inoculation. Initial lesions were typical pyogranulomas with central caseous necrosis, whereas later lesions consisted of connective tissue, mononuclear cells, abundant neutrophils, and liquefactive necrosis. Infected alpacas had detectable serum antibody titers starting on day 16 that persisted until day 93 after inoculation. Sham-inoculated alpacas did not develop serum antibody titers, clinical signs of infection, or lesions. Conclusions and Clinical Relevance - Alpacas inoculated with C pseudotuberculosis developed abscesses at the inoculation site and internally in the renal lymph nodes, without lung lesions. Corynebacterium pseudotuberculosis isolates from llama and alpaca origin were found to be pathogenically indistinct.