A growing body of evidence indicates that toxic contamination, both indoor and outdoor, negatively affects sociocultural systems and that this in turn affects the social and psychological responses to the contamination. Using secondary case studies and primary survey, interview and observation data from three toxic contamination situations, this paper conceptualizes and summarizes the findings to date. We argue that using a sociocultural perspective helps us to understand much of the seemingly inexplicable behavior that accompanies cases of toxic contamination. Using examples from primary and secondary case studies, four areas in which the sociocultural system affected by toxic contamination can influence the outcome of the response are described: a) engineering options may be frustrated by sociocultural systems; b) communications may be frustrated by sociocultural systems; c) cultural images and social structural patterns of space usage can affect response; and d) sociocultural systems can affect medical outcomes. Given the nature of sociocultural systems and human behavior, measuring the relationship between contamination, social response, and individual behavior is difficult. An example of one approach using the concept of alienation is discussed, wherein linkages have been found between toxic contamination, alienation, and psychological coping difficulties. Implications for professionals responding to toxic contamination cases are also discussed. We conclude that a sociocultural perspective provides a necessary complement to medical and engineering perspectives if we are to fully understand human reactions to toxic contamination and move toward alleviating human health problems associated with these risks.