The first two cases of Penicillium marneffei infection in humans were reported in 1959 and 1973. There had been no additional clinical reports of penicilliosis marneffei, until the five new cases of human infection described in this paper, the first from Thailand. The patients, three of whom died, came from various parts of the country. Their common clinical manifestations were fever and generalized lymphadenopathy, with multiple soft tissue, bone, joint and pulmonary involvement. Pericarditis with effusion was also seen. The diagnosis was established by isolating and identifying a dimorphic Penicillium species that produced a soluble red pigment in its mycelial form. The histopathologic features of the lymph nodes and bone marrow were similar to those of histoplasmosis capsulati. However, the yeast-like tissue form of P. marneffei divides by fission; that of Histoplasma capsulatum by budding. Treatment with amphotericin B was effective when this antifungal antibiotic was administered early in the course of the disease.