A cyclic adenosine monophosphate binding abnormality in psoriatic erythrocytes that could be corrected by retinoid treatment has been reported. It was tested whether this binding abnormality is specific for psoriasis and the effects of treatment were compared with etretinate, cyclosporine A, or anthralin on 2-(3)H-8-N(3)-cyclic adenosine monophosphate binding to the regulatory subunit of protein kinase A in erythrocyte membranes. One hundred and fifteen individuals were evaluated, including: (i) 34 healthy persons; (ii) 15 patients with nonatopic inflammatory skin diseases (eczema, erythroderma, tinea, Grover's disease, erysipelas, urticaria); (iii) eight with other dermatoses mediated by immune mechanisms (systemic lupus erythematosus, lichen planus, necrotizing vasculitis, erythema nodosum, systemic sclerosis); (iv) 14 with generalized atopic dermatitis; and (v) 44 with psoriasis vulgaris clinically assessed by Psoriasis Area and Severity Index. In psoriasis, the course of the binding of 2-(3)H-8-N(3)-cyclic adenosine monophosphate to erythrocytes was measured in nine patients during a 10 wk treatment with etretinate, in 21 patients during a 10 wk treatment with cyclosporine A, and one patient under topical treatment with anthralin for 4 wk. We found the following femtomolar binding per mg protein: (i) healthy persons (1064 +/- 124, mean +/- SD); (ii) nonatopic inflammatory skin diseases (995 +/- 103); (iii) immune dermatoses (961 +/- 92); (iv) atopic dermatitis (960 +/- 110); and (v) psoriasis (645 +/- 159; p < 0.0001 compared with nonpsoriatics, Mann-Whitney U test). Treatment of psoriasis with etretinate, cyclosporine A, or anthralin normalized the binding of cyclic adenosine monophosphate, which was inversely correlated to the Psoriasis Area and Severity Index score. It was concluded that the decreased binding of cyclic adenosine monophosphate to protein kinase A in erythrocytes is specific for psoriasis and normalizes after successful treatment.