This is the first description of an economically important disease of intensively reared Pangasius hypophthalmus from the Mekong Delta. Major presenting signs included an increase in mortality that would not respond to treatment, and at necropsy, the presence of numerous white necrotic and pyogranulomatous foci throughout the viscera, notably in spleen, liver and kidney. Despite the confounding presence in earlier samples of numerous, primarily renal, myxosporean parasites, the common denominator amongst these and samples from eight subsequently sampled sites was the presence of moderate-to-large numbers of bacilli in all typical lesions. These bacteria were subsequently isolated and tentatively identified as a Bacillus sp. Pilot studies experimentally reproduced similar lesions approximately 7 days following intraperitoneal injection of the bacteria.