A light and electron microscopic investigation of pseudomembranous candidiasis in HIV infection was undertaken as there is little data available on the ultrastructural features of the invasive phase of Candida in this disease. On examination of biopsy specimens of four patients, histopathology revealed the classic features of superficial candidiasis, including hyphal penetration down to the spinous cell layer, parakeratosis, acanthosis and spongiosis of the infected, superficial epithelium. However, in one case, hyphae traversed the entire epithelium and crossed the basal membrane, invading the adjacent connective tissue. Ultrastructural investigations revealed initial hyphal penetration through the intercellular spaces, possibly demonstrating thigmotropism. However, hyphal penetration was not solely confined to intercellular spaces, as some specimens demonstrated hyphal elements traversing both the cytoplasm and the nuclei of the spinous cells. In these areas of the epithelium appressoria-like appendages were often found at the hyphal tip. These phenomena, commonly described in plant fungi, have rarely been described in human material. Pools of desmosomes were seen in the vicinity of the hyphal pathways, implying that the penetration procedure is associated with detachment and congregation of desmosomes, possibly by enzymatic means. Interestingly, the host immune response to fungal invasion appeared to be minimal, as no immune-effector cells were seen closely associated with either the blastospores or the hyphae in any of the tissues examined. Whether the foregoing events are exaggerated by the abortive immune response seen in HIV-infected patients, or common in immunocompetent individuals during candidal invasion of epithelia, needs to be ascertained by further studies.