Epidermal Langerhans cells (LC) disappear during photochemotherapy (PUVA) with 8-methoxypsoralen (8-MOP) and long wavelength ultraviolet (UV-A) radiation. The time course of their disappearance during treatment and their reappearance after its completion was followed. Langerhans cells lost ATPase activity before they disappeared by ultrastructural criteria: thus 90% of ATPase-stained cells had disappeared after seven treatments (2 weeks) whereas it was only after fifteen treatments (5 weeks) that they were seen to be reduced on electron microscopy. Their numbers remained low throughout the course of treatment but they had returned to normal by 3 weeks after cessation of therapy. Since PUVA lamps also emit traces of medium wavelength UV (UV-B) the separate effects of UV-A and UV-B in the presence and absence of 8-MOP were examined. Within the dose range normally used for therapy, the LC disappeared only with the combination of UV-A and 8-MOP.