Platelet GTP binding protein (G protein) in 25 alcoholics with a first-degree alcoholic relative (family history positive alcoholic; FHP), in 25 alcoholics without alcoholic relatives (family history negative alcoholic; FHN) and in 25 controls without alcoholic relatives was investigated to determine whether this protein is a trait marker for alcoholism. The alcoholic subjects met DSM III-R criteria for alcohol dependence and had been abstinent from alcohol for at least one year. Lowered platelet guanine nucleotide (GppNHp)-stimulated adenylyl cyclase (AC) activity and reduced sensitivity of AC to ethanol were recognized in FHP but not in FHN. Remarkable reduction in ethanol enhancement of functional photoaffinity GTP (azidoanilido GTP; AAGTP) binding to Gs alpha and Gi alpha in platelet membrane was observed in FHP but not in FHN. A quantitative reduction in Gs alpha and GsH alpha (high molecular weight Gs alpha) levels as assessed by immunoblotting was seen in platelet membrane from FHP but not from FHN. These results indicate that the characteristic of platelet G protein may be used as a trait marker for alcoholism.