To elucidate the mechanisms that are involved in the decrease of ceramide levels in atopic dry skin and in aged skin, we examined both the activities of beta-glucocerebrosidase, which is a major enzyme in ceramide production, and of ceramidase, which is an essential enzyme in ceramide degradation, in the stratum corneum of atopic dry skin and aged skin. The specimens of the stratum corneum of forearm skin were obtained by tape-stripping from 61 healthy volunteers and 23 patients with atopic uninvolved skin. The beta-glucocerebrosidase activity in the stratum corneum extracts was estimated using fluorescent 4-methylumbelliferyl-beta-D-glucopyranoside as the substrate. Ceramidase activity was determined using 14C-palmitoylsphingosine as the substrate. Among the atopic skin samples, neither beta-glucocerebrosidase nor ceramidase activities were different from those of age-matched healthy controls. Nor was the beta-glucocerebrosidase activity deficient in the aged skin samples as compared to that seen in samples from the young, healthy group. In contrast, there was an age-related upregulation in ceramidase activity. The results indicate that the decrease of ceramides in atopic dry skin may not be accompanied by reduced synthesis or by enhanced degradation, each of which is primarily attributable to the above two enzymes, respectively. The pathogenesis of aged dry skin can be explained, at least partially, in terms of elevated ceramidase activity, which results in a disturbance of the lamellar structure of the stratum corneum lipids.