Previous studies demonstrated a reduced G(s)-protein stimulated adenylyl cyclase activity in the brain and blood cells of alcoholics. We investigated this phenomenon in platelets of children of alcoholics (COA), i.e., of children at high risk for the acquisition of alcoholism and (as yet) not regularly consuming alcohol. G(s)-protein mediated stimulation of adenylyl cyclase by 30 mM NaF and 50 μM forskolin stimulated adenylyl cyclase activity were assessed in platelet membranes of 23 (male and female) COA and 20 control children. G(s)-protein stimulated cAMP production by NaF, unlike that induced by direct stimulation of adenylyl cyclase with forskolin, in platelet membranes of COA was profoundly lower than in platelet membranes of control children. Moreover, such a reduced G(s)-protein functioning was only observed in platelet membranes of COA with a multigenerational family history of alcoholism. A reduction of G(s)protein stimulated adenylyl cyclase activity, in platelets may represent a sensitive and gender-independent trait marker for predisposition to alcoholism, rather than a state marker for alcoholism.