Cells of Candida albicans WO-1 switch frequently and reversibly between two colony-forming phenotypes, white and opaque. In the white form, budding cells appear similar to those of most other strains of C. albicans, but in the opaque form, budding cells are larger, are bean shaped, and possess pimples on the wall. These pimples exhibit a unique and complex morphology. With scanning electron microscopy, a central pit can be discerned, and in many cases, a bleb can be observed emerging from the pimple center. With transmission electron microscopy, channels are evident in some pimples and vesicles are apparent under the pimple in the cytoplasm, in the actual wall of the pimple, or emerging from the tip of the pimple. A large vacuole predominates in the opaque-cell cytoplasm. This vacuole is usually filled with spaghettilike membranous material and in a minority of cases is filled with vesicles, many of which exhibit a relatively uniform size. An antiserum to opaque cells recognizes three opaque-cell-specific antigens with molecular masses of approximately 14.5, 21, and 31 kilodaltons (kDa). Absorption with nonpermeabilized opaque cells demonstrated that only the 14.5-kDa antigen is on the cell surface; indirect immunogold labeling demonstrated that it is localized in or on the pimple. The possibility is suggested that the vacuole of opaque cells is the origin of membrane-bound vesicles which traverse the wall through specialized pimple structures and emerge from the pimple with an intact outer double membrane, a unique phenomenon in yeast cells. The opaque-cell-specific 14.5-kDa antigen either is in the pimple channel or is a component of the emerging vesicle. The functions of the unique opaque-cell pimple and emerging vesicle are not known.Candida albicans and related species are capable of switching at high frequencies between a number of general phenotypes distinguishable by colony morphology (18,20,21,24). There are a number of different switching systems in the species C. albicans and Candida tropicalis, which differ from one another in phenotypic repertoire (18,20,21,26,27). Thus far, all of the systems tested share characteristics of high-and low-frequency modes of switching, heritability, reversibility, a limited number of phenotypes, and stimulation by low doses of UV irradiation (24,25). One of these switching systems, the white-opaque transition, involves a dramatic change not only in colony morphology but also in the basic phenotypes of cells in the budding growth form (1,2,19,21). In the white phase, cells produce smooth white colony domes in all respects similar to those produced by most other strains of C. albicans (2,21 large and sometimes multiple vacuoles (21) as well as unique pimples on the mature cell wall (1, 2). In addition, it has been demonstrated that opaque cells possess one or more opaquecell-specific antigens distributed in the cell wall in a punctate fashion similar to pimple distribution (1, 2).We present here scanning electron microscopy (SEM) and transmission electron microscopy (TE...