Keratinocyte differentiation in psoriasis was examined using a panel of monospecific monoclonal antibodies to keratins (K), including two recently dcveloped monoclonal antibodies raised to carboxy terminal peptides of K6 (LL020) and Kl6 (LL025). Keratinocytes from normal skin, untreated psoriatic plaques and non‐lesional psoriatic skin, were cultured using multiple in vitro Systems. Timelapse cinephotography was used to measure the intermitotic time of normal and psoriatic keratinocytes in both low calcium‐defined and serum‐containing media. The intermitotic time did not differ significantly between psoriatic and normal keratinocytes. Keratin expression of psoriatic and normal keratinocytes in vitro was examined by both gel electrophoresis and immunocytochemistry. K6. K16 and Kl7 were detected suprabasally in all culture Systems in vitro, but only in interfollicular psoriatic epidermis in vivo. and not in normal skin. Small subpopulations of keratinocytes expressed simple epithelial keratins K7, K8, Kl8 and K19 in cultures on plastic Substrates, but these keratins were absent in skin equivalents of normal or psoriatic skin. No psoriasis‐spesfic pattern of differentiation was found in vitro. As the K6 peptide antibody reacted with basal cells of normal skin. probably due to K5 cross‐reactivity. K16 expression determined by LL025 was found to be the most sensitive indicator of the psoriatic state of differentiation. and this antibody is recommended for future work on psoriasis. Kl7 had a distinct pattern of tissue distribution in normal skin: Kl7. but not K16. was present in basal myoepithelial cells in sweat glands. and the dccp outer root shealh. but Kl 7 distribution parallelcd that ol'Klfi in suprabasal psoriatic epidermis. As keratins K6. Kid and Kl 7 are expressed in keratinocyte hyperproliferation. when high Ievels of certain cytokines are also expressed. the role of growth factors and regulalory nuclear transcription factors in the control of K6, K16 and Kl7 cxpression in psoriasis requires further study, in order to provide insight into the relationship between proliferation and differentiation.