We investigated skin biopsies from pemphigus vulgaris (PV) patients by light, fluorescent and electron microscopy in order to study the ultrastructural appearances of epidermis at the pre-acantholytic stage. The biopsies were obtained from uninvolved forearm skin in 10 patients with PV in the acute stage of the disease, from perilesional skin of the same patients as well as from the forearm skin of 10 healthy subjects. Light microscopy showed no pathological changes in clinically uninvolved skin of pemphigus patients. Direct immunofluorescence confirmed the presence of IgG auto-antibodies fixed in intercellular space of the spinous-cell layer of uninvolved skin. Electron microscopy of the uninvolved skin biopsies revealed the following changes: disintegration of desmosomes of spinous cells with their replacement by finger-shaped protrusions of cytoplasm; clarification of the nuclear matrix; widening of the perinuclear slit; an increased number of secondary lysosomes in cells; oedema and swelling of mitochondria with destruction of their cristae. The cells retained their polygonal shape and the intercellular distance did not increase. We conclude that at the pre-acantholytic stage the breakage and dissolution of desmosomes precedes the increase in the intercellular space.