Keratinocytes and melanocytes cultured from guinea-pig epidermis were studied with scanning, transmission and high voltage electron microscopy to characterize the surface and internal morphology. Keratinocytes exhibited contact-inhibition and a range of surface structures consistent with cell-cycle dependent changes. Stereoscopic analysis of high voltage electron micrographs indicated regular oval nuclei with nucleoli at different depths, while thin sections revealed local channels in the nuclei. Secondary cultures differed from primary cultures in the disorder of the microfilaments, in the failure to form desmosomes, and in the failure of melanocytes to persist in culture. The beaded surface of melanocytes was indicative of underlying melanosomes that were seen in high voltage micrographs. Melanocytes were rounded with moderate ruffles or were dendritic with ruffles on the termini. These findings are discussed in relation to the observational techniques and in relation to modes of locomotion of and pigment transfer to epidermal cells.