Previous studies have demonstrated elevated cyclic-AMP-specific phosphodiesterase (PDE) activity in mononuclear leukocytes (MNL) from patients with atopic dermatitis (AD). We questioned whether increased kinase activation could account for this observation. In these studies, we measured abnormally lower basal calcium/phospholipid-dependent protein kinase (PK-C) phosphorylation in MNL from patients with AD. Basal cAMP-dependent protein kinase (PK-A) phosphorylation was concomitantly higher in MNL from patients with AD. These results are in agreement with earlier reports that PK-A activity may have a negative influence on PK-C activity in certain cell systems. Stimulation with the H1-histamine agonist, thiazolylethylamine (TEA), of MNL from normal donors but not patients with AD, resulted in statistically significant increases in PK-C phosphorylation. This implies receptor down regulation or functional desensitization in AD cells. Altered basal protein kinase phosphorylation and abnormal response to selective histamine agonists seen in MNL from patients with AD could explain elevated PDE activity.