Regional separatism in Mexico, especially in the north, has been one of the most persistent and difficult to explain problems in the historiography of the Mexican Revolution, 1910-1920. It is well known that men of the north (norteños) made the Revolution, in large part, and finally succeeded in winning political power. But norteños, even those who followed Francisco I. Madero and after his fall, continued the struggle under the Constitutionalist banner, failed to agree among themselves either on their aims or their leaders. Leaving aside the questions of motive and ultimate objectives of the major separatists—Pascual Orozco and Francisco “Pancho” Villa in Chihuahua, Esteban Cantú Jiménez in Baja California Norte, and the triumvirate of Alvaro Obregón, Plutarco Elías Calles and Adolfo de la Huerta in Sonora—the question of how they financed their independent courses during and after the Constitutionalist victory remains. The following pages represent a preliminary inquiry into the role of illicit drug trafficking between Mexico and the United States in the era of the Mexican Revolution and its contribution to regional autonomy. Patterns and practice of medical and personal usage, as well as supply and demand in both countries are considered for opium, its derivatives, cocaine and alcoholic beverages, along with the gambling and prostitution associated with this trade. The interaction of all these activities and the governmental revenue derived from them, are treated in detail for Baja California Norte. The combined evidence clearly shows the potential governmental income from this clandestine traffic and strongly suggests the hypothesis that illicit trafficking provided a financial base for regional autonomy and separatism during the Revolution.