Penicillium marneffei is a common cause of opportunistic fungal infection in patients with AIDS in Thailand. The diagnosis of penicilliosis is easily made when typical skin lesions appear but is frequently missed in their absence. We therefore attempted to identify noncutaneous indicators of P. marneffei infection in order to provide early curative treatment. We recognized a characteristic syndrome in six AIDS patients with penicilliosis involving primarily the liver but not the skin who presented with fever of short duration, hepatomegaly, and markedly elevated serum alkaline phosphatase levels. The diagnosis was confirmed by demonstrating the causative organism in the liver or in the blood. Increased awareness of hepatic penicilliosis and more-rapid diagnostic methods are needed to reduce the high mortality rate associated with this syndrome. P. marneffei is predominantly an Asian pathogen, but as a result of international travel, the need for increased awareness of penicilliosis is worldwide.