With the advent of non-fluorinated double esters the spectrum of topical dermatotherapy with glucocorticoids seems to have broadened to include safer congeners. To assess the atrophogenicity potential of glucocorticoids, high-frequency ultrasound has been proposed. In a comparative trial using the DUB 20 system, 24 healthy volunteers applied hydrocortisone aceponate, the corresponding vehicle, prednicarbate ointment and betamethasone-17-valerate ointment over a period of 6 weeks. While both hydrocortisone aceponate and prednicarbate ointment induced no significant reduction in skin thickness, the onset of epidermal-dermal thinning with betamethasone-17-valerate was early and the extent marked. These findings imply an increased therapeutic index with the non-fluorinated double esters.