Lombazole, an antimicrobial agent of the imidazole class, induced profound ultrastructural changes in Staphylococcus epidermidis and Candida albicans, as observed by freeze fracture electron microscopy. In S. epidermidis cells, the primary effect on ultrastructure was characterized by a distinct change in the morphology of the plasma membrane. Secondary effects of lombazole were cell wall thickening, accumulations of lipidlike material, abnormal cell division, severe change of shape, separation of the plasma membrane from the cell wall, and disruption of cells. The alterations in C. albicans were characterized by the deformation of and a decrease in the number of invaginations in the protoplasmic fracture face and corresponding ridges on the exoplasmic fracture face and by separation of the plasma membrane from the cell wall, leaving a gap which frequently contained small vesicles. Moreover, a considerable thickening of the cell wall occurred at localized regions. These structural alterations are discussed in relation to biochemical changes which may correlate with these phenomena.