In normal skin, proliferation and differentiation are tightly coupled in order to maintain normal architecture in a continually renewing tissue. The temporal and spatial relationships between these two processes in normal, psoriatic, pre-neoplastic and neoplastic skin were investigated by a double immunolabelling technique with Ki67 as a marker of proliferation and involucrin as a marker of terminal differentiation. In normal skin, expression of the two antigens was strictly spatially segregated. In the abnormal, the proportions of cells expressing the antigens were increased with some loss of the spatial segregation, while small numbers of cells showed dual expression suggesting loss of the normal control between proliferation and differentiation. However, the quantitative ratio of proliferation to differentiation in psoriatic and pre-neoplastic skin was similar to the normal; transition to an invasive phenotype, however, was associated with a reversal of this ratio, and this correlated well with the degree of histological differentiation.