Penicillium marneffei (P. marneffei ) infection usually occurs with skin, bone marrow, lung or hepatic involvement. However, no cases of P. marneffei infection with chylous ascites have been reported thus far. In this report, we describe the first case of acquired immune deficiency syndrome (AIDS) which has been complicated by a P. marneffei infection causing chylous ascites. We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with amphotericin B for 3 mo, while receiving concomitant therapy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei . The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 mo. P. marneffei should be considered in the differential diagnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of systemic infections with P. marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen. However, no cases of P. marneffei infection with chylous ascites have been reported thus far. In this report, we describe the first case of acquired We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with amphotericin B for 3 mo, while receiving concomitant therapy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei. The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 months. P. marneffei should be considered in the Differential diagnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of syste mic infections with P. marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.