We have measured the RNA and DNA content and examined cell surface characteristics of human epidermal cells derived from normal skin, and lesional and nonlesional areas of psoriatic skin prior to and following treatment on a modified Goeckerman protocol. Our results show that cells from active psoriatic lesions contain greater numbers of basal keratinocytes when compared with either nonlesional skin from the same patients or skin from healthy volunteers and individuals with other inflammatory skin lesions. Follow-up measurements 2-3 weeks after the initiation of therapy showed that the numbers of basal keratinocytes in resolving psoriatic lesions had decreased and approached normal levels. Multiparameter RNA/DNA flow cytometric analysis on parallel samples from the same psoriasis patients revealed an increased growth fraction and proportion of cycling cells in both the nonlesional and lesional skin compared with controls. Furthermore, the cellular RNA content was elevated in lesional psoriatic skin when compared with either nonlesional or normal skin. Flow cytometric examination of nonlesional and lesional epidermal cells obtained 2-3 weeks after the commencement of therapy revealed that the growth fraction and mean RNA content of the keratinocytes from resolving psoriatic plaques decreased in response to therapy. In contrast, the proportion of keratinocytes within the S + G2 + M phases of the cell cycle remained elevated. These data indicate that "uninvolved" psoriatic skin exhibits characteristics more closely resembling lesional psoriatic skin than normal skin. The results further suggest that quantitation of cellular RNA content and basal cell number might be sensitive indicators of early treatment response in psoriasis.