The ultrastructural pattern of human hair infection by Piedraia hortae in vivo has been studied. The fungus destroyed the cuticular layers of the hair and was able to penetrate deeply into the cortex. The course of destruction of human hair is described and compared with that produced by other fungi. Two well-defined types of cortex digestion were characterized. The slow rate of keratin degradation at the cortex together with the compacted stromatic organization of the nodules are argued as the main reasons that guarantee the long survival of the fungus, and therefore the chronic course of the disease. The data provided in this paper may help to understand the mechanisms that regulate the pathogenicity of this fungus.