cAMP and cGMP production was determined in normal and psoriatic (involved or uninvolved) epidermis. After homogenization, epidermal strips were incubated with saturating concentrations of ATP or GTP, respectively, for cAMP and cGMP production. Cyclic nucleotides were measured by radioimmunoassay before and after 5, 10,20 min of incubation. The kinetics of cAMP and cGMP production were linear during the 20 min of incubation. Comparison of normal skin, uninvolved and involved psoriatic skin, prior to and after 20 min of incubation showed the following results: cAMP levels were significantly higher in normal skin than in psoriatic skin at zero time (p < 0.01) and after incubation (p < 0.05). cGMP levels were not significantly different in the three tissues at zero time. After incubation, psoriatic involved epidermis exhibited a higher production of cGMP than normal skin (p < 0.05). Thus, the ratio cAMP/cGMP was higher in normal skin than in psoriatic skin at the basic level (p < 0.05) and after incubation (p < 0.01). These results indicate an imbalance in cyclic nucleotides metabolism in psoriatic skin without a significant difference between uninvolved and involved epidermis.