In this study, we employed a high-frequency ultrasound system to measure the epidermal thicknesses of psoriasis plaques and normal skin in vivo. Eighty-four percent of the ultrasound measurements fell within the range of epidermal thickness determined by histology. The average thickness of untreated psoriasis measured by ultrasound was significantly greater than that of either treated psoriasis or normal skin. Ultrasound measurement of thickness was consistent with clinical assessment. Ultrasound measurements also demonstrated known variations in epidermal thickness by body site. Further development is needed to obtain measurements that are fully representative of the epidermis.