Most species of Penicillium are considered relatively benign with respect to causing human disease. However, one species, P. marneffei, has emerged as a significant pathogen particularly among individuals who live in Southeast Asia and are concurrently infected with the human immunodefiency virus. While environmental and epidemiological studies have yet to resolve the reason for the heightened virulence of P. marneffei, one characteristic does distinguish this fungus from other Penicillium species. Whereas the latter grow as monomorphic moulds bearing typical asexual propagules (conidia), P. marneffei is thermally dimorphic. At room temperature, P. marneffei exhibits the morphology characteristic of the genus. In contrast to other Penicillia, though, P. marneffei grows as a yeast-like entity (arthroconidium) when found in diseased tissue or cultivated at 37 °C. Studies in our laboratory have focused on the differential gene expression between the mould and arthroconidial phases. Many of the genes whose expression differs during mould-to-arthrocondium transition are related to energy metabolism. A better understanding of gene expression during morphogenesis in P. marneffei may help detect unique target sites or cellular processes that can be exploited in the development of antifungal agents or immunomodulation therapies.