Previous studies of the polyamines and their biosynthetic enzyme ornithine decarboxylase (ODC) in psoriatic skin have revealed several abnormalities, including significantly elevated ODC activity. Retinoids have also been shown to modulate polyamine biosynthesis and inhibit ODC activity after different stimuli in various cell and tissue systems. The effect of etretinate has been studied on ODC activity in involved and uninvolved psoriasis skin. Increased ODC activity was found in pretreatment samples from both involved and uninvolved psoriatic skin compared with normal volunteers. Etretinate treatment significantly reduced ODC activity in both involved and uninvolved skin in psoriatics to a similar level of activity before any improvement in clinical appearance was noted. Inhibition of epidermal ODC activity in psoriasis may represent one mechanism of retinoid action on the abnormal skin of psoriasis.