The main objective of this investigation was to study the influence of drug dependence on platelet monoamine oxidase (MAO) activity in the presence and absence of alcoholism. One hundred and thirteen admissions to alcohol and drug treatment facilities participated in the study. Twenty-six met the criteria for alcoholism (group I), seventy-eight subjects were alcohol-/cocaine- and cannabis-dependent (group II), and the remaining nine were patients with DSM-III-R diagnosis of cocaine addiction (group III). MAO activity was assayed radiochemically with [14C]tyramine as a substrate (221 microM). The results of this study showed that platelet MAO activity [nmol of product formed x (mg protein)-1 x hr-1] (mean +/- SE) was significantly (p < 0.01) lower in all of these subjects (group I, 5.50 +/- 0.80; group II, 3.90 +/- 0.50; group III, 4.3 +/- 1.60) as compared with controls (14.85 +/- 1.13). Measurements of platelet MAO activity may provide us with a reliable biochemical marker for alcoholism and perhaps addiction to other substances of abuse (i.e., cocaine).