Hydroxyethyl starch (HES) is a colloidal infusion fluid that has for a long time been used in emergency situations and to improve impaired blood perfusion. In the last few years there have been numerous reports about treatment resistant pruritus, often persisting for months, after HES infusion. We investigated the intracellular uptake of HES in the skin, special attention being focused on associated pruritus.Skin biopsies were obtained from 120 patients (120 men, 35 women) and examined immunohistochemically and for their ultrastructure. Three patients had received various HES preparations, while 22 had been given dextran. Five patients who had received no infusions served as controls.All patients given HES had lysosomal deposits in the histiocytes, some of them also in cutaneous epithelium and endothelium. The extent of lysosomal storage correlated with the amount of infused HES and the interval between biopsy and last HES infusion. Consecutive biopsies in some cases demonstrated a definite decrease over the years of HES deposits in the vacuoles. This suggests that HES is regularly metabolized in the skin. Pruritus after high cumulative doses of HES was closely correlated with HES deposition in cutaneous nerves.These results emphasize the need for starch derivatives that can be better metabolized and for better adapted infusion schedules to reduce the high incidence of pruritus.