The results of the very few histochemical studies that have been performed so far on the lectin-binding profile of normal human epidermis are mostly controversial; thus, the carbohydrate residue composition of the cell surface in the latter still remains in dispute and the possible alterations in the epidermal lectin-binding profile are unknown. To investigate the influence of age on the carbohydrate residue composition of the cell surface in unexposed normal human epidermis by means of lectin histochemistry. Biopsy specimens obtained from the sun-protected (unexposed) buttock skin, divided into 5 age groups of 18 subjects each, were fixed in buffered formalin (10%) and embedded in paraffin. 4-mum sections were processed for histochemistry using a panel of six biotinylated lectins. In the unexposed normal human epidermis the concentration and distribution of cell surface beta-D-galactose, D-galactose-beta-(1,3 N-acetylo-D-galactosamine), beta(1,4 D-N-acetylo-D-glucosamine) and alpha-D-N-acetylo-D-galactosamine were almost identical in all age groups, whereas those of alpha-D-mannose, alpha-D-glucose and alpha-L-fucose revealed significant age-related differences. These findings may be due to an age-related decline in synthesis and/or transport of monosaccharides from the cytoplasm to the surface of epidermal cells. Thus, the corresponding lectins concanavalin A and Ulex europaeus agglutinin-I can only be used in comparative histochemical studies of the carbohydrate residue composition of the cell surface in the normal and pathological epidermis of individuals of the same age, whereas Ricinus communis agglutinin-I, peanut agglutinin, wheat germ agglutinin and Dolichos biflorus agglutinin, whose binding to carbohydrates is not affected by aging can be used in histochemical studies of carbohydrate residue composition of the cell surface in the normal and pathological epidermis in human subjects of any age.