Abstract The basal and stimulaed intracellular cyclic AMP (cAMP) levels of peripheral blood mononuclear cells (PBMC) of 16 control subjects and 14 patients with systemic lupus erythematosus (SLE), all fulfilling the ARA criteria, were studied. No significant difference in basal cAMP level was observed between SLE patients and controls. SLE lymphocytes (both active and inactive) elicited a diminished response to aminophylline and prostaglandin E 2 (PGE 2). No correlation was seen between disease activity and either baseline cAMP levels or response to these stimulators. We suggest an intrinsic (not disease activity-related) impairement of the adenylate cyclase-dependent regulatory mechanism in the PBMC of SLE patients, which may result in a defective IL-2 production and IL-2 dependent biological functions.