The development of skin lesions in patients with dermatitis herpetiformis after the withdrawal of their dapsone therapy was studied with the electron microscope. In control biopsies from patients prior to cessation of treatment, membrane-bound vacuoles were found beneath the basal lamina of the epidermis as previously described. After dapsone withdrawal, there was an apparent increase in the number of vacuoles and occasionally several vacuoles appeared to have coalesced forming an early blister. At this stage, the basal lamina and associated hemidesmosomes were normal although in places there were small discontinuities in the basal lamina. Where the reaction was more intense, vacuoles and cells, mainly eosinophils, were embedded in fibrin de posits. Above this, the basal lamina was usually disrupted with involvement of the basal epidermal cells. These results suggest that the vacuoles do play a part in the formation of the pathological lesion in dermatitis herpetiformis. In addition, the basal lamina is shown to be only secondarily involved. The nature of the vacuoles has still to be elucidated.