• A double freeze-thaw cryoapplication to the conjunctiva was used to treat the flat intraepithelial proliferation of atypical melanocytes in five patients. Electron microscopy of six paired biopsy specimens taken before and after cryotherapy showed in all specimens rupture of plasmalemmas of intraepithelial melanocytes and release of cytoplasmic debris into the intercellular space. In four patients the plasmalemmas of the squamous cells (keratinocytes) generally remained intact after nitrous oxide treatment (temperatures reaching -20 °C by thermocouple monitoring), but these cells frequently displayed dissolution of intercellular desmosomes and hemidesmosomal contacts with the basement membrane. In one patient treated with liquid nitrogen, both the squamous cells and the melanocytes were irreversibly damaged at temperatures of -40 °C. These ultrastructural data establish that there is a selective sensitivity of atypical intraepithelial conjunctival melanocytes to freezing at temperatures below -20 °C.