We have compared the staining patterns of Ulex europeus agglutinin (UEA) I-FITC and Helix pomatia agglutinin (HPA)-FITC on normal and psoriatic epidermis in order to follow the production of the binding sites as a function of maturation. We have further characterized them with respect to solvent extraction and enzyme digestion. The bandlike pattern of membrane staining by UEA I in the upper spinous and granular layer cells of normal epidermis is lost in psoriasis. Instead there is a fainter cytoplasmic staining which is largely sensitive to chloroform/methanol extraction, and thus presumably is glycolipid in nature. Epidermal binding of HPA to normal skin sections is mainly seen in cell membranes. It spares the basal layer and then increases from the suprabasal region to the granular layer. HPA staining in the spinous layer is destroyed by extraction with Triton X-100. In contrast, binding to the membranes of cells in psoriatic epidermis is triton-resistant. The result indicates the production of a component early in the maturation pathway which has no counterpart in normal skin. HPA binding to the spinous cells of symptomless skin from psoriatic patients shows decreased sensitivity to Triton X-100 by comparison with normal. The results are discussed in terms of changes in the pathway of keratinocyte maturation in psoriasis.