A 5-yr-old, intact male red ruffed lemur (Varecia rubra) presented for evaluation as the result of a 1-wk history of lethargy and hyporexia. Physical examination findings included thin body condition, muffled heart sounds, harsh lung sounds, and liquid brown diarrhea. Complete blood count and serum biochemistry showed an inflammatory leukogram, mild hyponatremia, and mild hypochloremia. Orthogonal trunk radiographs revealed a severe alveolar pattern in the right cranial lung lobes with cardiac silhouette effacement. Thoracic ultrasound confirmed a large, hypoechoic mass in the right lung lobes. Fine-needle aspiration of the lung mass and cytology revealed fungal yeast organisms, consistent with Blastomyces dermatitidis. Blastomyces Quantitative EIA Test on urine was positive. Postmortem examination confirmed systemic blastomycosis involving the lung, tracheobronchial lymph nodes, spleen, kidney, liver, cerebrum, and eye. To the authors' knowledge, this is the first report of blastomycosis in a prosimian species.