The exact nature of the events which may predispose a person to substance abuse is not known. This paper provides a theoretical discussion and review which emphasizes three contexts which have been shown to predispose on individual to drug abuse: (1) prenatal exposure to a given substance; (2) environmental conditions present upon first exposure to an abuseable substance; and (3) the environment in which a person lives and functions. Support for each of these factors in combination as probable causal factors in substance abuse is garnered from both human and nonhuman investigations. Research findings are discussed concerning such factors as Fetal Alcohol Syndrome, the social context in which people are first exposed to the use of drugs and alcohol, contextual reinforcers and constraints, and excessive drug abuse as adjunctive to schedule-induced behavior. Drug abuse is therefore considered as an interaction between both environmental and physiological variables. The paper concludes by calling for multi-generation testing to evaluate the role of genetic influences in predisposing drug abuse. References are included. (Author/TE)