The differentiation of skin during foetal development, the maturation of cells in the normal adult epidermis, and the alterations, occurring in psoriatic lesional epiderms have been investigated using biochemical and immunocytochemical methods. These were used as appropriate on frozen sections, separated epidermis, dispersed keratinocytes and subfractions of keratinocyte populations, prepared directly from epidermis or epidermal cultures. Various techniques were used to separate dispersed keratinocytes, and these were monitored by light microscopy, electron microscopy and immunocytochemistry. The method most widely employed was Percoll density gradient centrifugation (PDGC) . A potential Fluorescence activated cell sorter (FACS) technique proved disappointing, but in a model system free flow cell electrophoresis (FFCE) separated basal cell populations and clearly has potential for use in man. Analysis of protein components was performed using 2DGEL with a conventional rod and a new flatbed method for the first dimension. various methods of protein detection were investigated. Silver staining proved to be the most useful for unlabelled proteins. Proteins labelled with 75Se or 35S methionine were detected by autoradiography. Glycoproteins were identified by lectin blotting of gels, by use of an enzyme hydrazide technique or by incorporation of tritiated sugars and subsequent fluorography or autoradiography. Hydrophobic proteins were extracted using a Triton X-114 phase shift method following by electrophoresis.