Morphological studies of the WISH cell line reveal an epithelioid cell type with some characteristics of both the original human amnion epithelium and a transformed state. WISH cells have a cytoplasm filled with microtubules; however, actin filament bundles are few, with actin localized at areas of cell contact and arranged diffusely through the cytoplasm, as viewed by indirect immunofluorescence. Fingerlike projections or short filopodia are observed connecting cells that grow in a closely apposed monolayer. Other surface features, as viewed by scanning electron microscopy, include microvilli and blebs. Transmission electron microscopy shows that WISH cultures consist of light or dark cells with organelles that include lipid droplets, abundant free ribosomes, tubular mitochondria, lysosomes, annulate lamellae, rough endoplasmic reticulum, 6-nm microfilaments, 10-nm intermediate filaments, and microtubules. Pleomorphic nuclei with multiple nucleoli and fibrillar nuclear bodies are common. Desmosomes and subsurface confronting cisternae connect cells. To our knowledge, these structural studies are the first to describe WISH and lead to subsequent investigation of the cell surface phenomenon of blebbing and surface charge in WISH and another human cell line.