In many cases of mycosis fungoides there is widening of the epidermal intercellular spaces (i.e., spongiosis) and papillary dermal fibrosis with minimal papillary dermal edema. Twenty biopsies of mycosis fungoides, stained with a modified colloidal iron procedure, were analyzed to substantiate the notion that the spongiosis resulted from the formation of an osmotic gradient because of intercellular acidic mucopolysaccharide deposition. In nineteen of twenty cases of patch-plaque mycosis fungoides, there was positive intercellular deposition of acidic mucopolysaccharides. In addition to the contribution of acidic mucopolysaccharides to the process of spongiosis, the biologic significance of epidermal mucin deposition is discussed. Mycosis fungoides should be added to the growing list of diseases in which there is epidermal mucinosis.