Published data (mainly from rodent skin) suggest a correlation between compounds which inhibit protein kinase C (PKC), have anti-inflammatory or antitumor characteristics and possess antipsoriatic potential. We have investigated the effects of topical application of sphingosine (a naturally occurring PKC inhibitor), isoquinoline (a component of coal tar which showed antipsoriatic capacities in the mouse tail model) and tannic acid (a plant phenol with antitumor activity) on human skin. In each case we have assessed (a) the level of induction of ornithine decarboxylase (ODC) following Sellotape® stripping as an indicator for potential PKC inhibition in vivo, and (b) its effects on the lesions of chronic plaque psoriasis. The control group consisted of 18 healthy volunteers, used for the ODC induction experiments (0.0/0.1/0.2 M sphingosine in ethanol, 100% coal tar and 0/50 mM tannic acid in acetone) and 17 psoriatic patients used for double-blind scoring of two randomly selected lesions (0.0/0.1 M sphingosine in ethanol, 0.0/0.2% isoquinoline in white vaseline/lanette wax cream 50%/50% and 0/10% tannic acid in lanette wax cream) and also for some of the ODC induction experiments (0.0/0.2% isoquinoline and 0/10% tannic acid). Biopsies were taken 8 h after stripping and ODC activity was assessed by measurement of 14CO2 release. Lesions were scored with a modified psoriasis area and severity index on days 0,7 (isoquinoline and tannic acid), 13 (sphingosine) and 21 (isoquinoline and tannic acid). Application of 0.1 or 0.2 M sphingosine resulted in a decrease of ODC activity of 52% and 66%, respectively (p 0.05). All compounds failed to show significant improvement of the psoriatic lesions. Therefore we may conclude that ‘theoretical’ antipsoriatic agents may be limited in practice by cytotoxicity and hence a narrow therapeutic index, poor penetration and lack of specificity. Further, a marked difference between the effects of these compounds on the skin of different species increases the difficulty of predicting antipsoriatic acti