This study explored the relationship between substance use and spirituality and religious participation with a multicultural sample of rural youths in the American Southwest. Logistic regression was used to determine the efficacy of spirituality and religious participation as predictors of never using alcohol, marijuana, and hard drugs. Although increased participation in religious activities predicted greater probability of never using alcohol, increased spirituality predicted greater probability of never using marijuana and hard drugs. The article concludes with a discussion of the implications of these findings for prevention programs, social work education, and research. Key words: adolescents; religious participation; rural populations; spirituality; substance use Federal data indicate that substance use appears to be an increasing problem among youths after reaching relatively low levels in the early 1990s; the possible exception was alcohol, which demonstrated a relatively stable pattern throughout the decade. Between 1992 and 1998 the self-reported current use of illicit drugs increased from 5.3 percent of youths ages 12 to 17 to 9.9 percent; self-reported rates of current marijuana use increased from 3.4 percent to 8.3 percent. The number of new cocaine users has increased from 4.1 million in 1991 to 10.8 million in 1997. Among youths, the recent rates of initiation to cocaine use are the highest since the early 1980s; for heroin the number of initiates is at the highest level since the early 1970s (Substance Abuse and Mental Health Services Administration [SAMHSA], 1999). A growing body of research has indicated that religiosity tends to be a protective factor for substance use by youths (Benson, 1992; Benson & Donahue, 1989; Donahue & Benson, 1995; Francis, 1997; Kutter & McDermott, 1997). However, most of the research has focused on religion rather than spirituality. With the growing realization that spirituality is a discrete construct separate from religion, calls have been made to explore the interaction between spirituality and substance use (McCarthy, 1995; Miller, 1998; Morell, 1996). Furthermore, research on the relationship between religiosity and substance use among youths commonly has used samples that consisted largely of non-Hispanic white youths or African American youths in urban or suburban settings. To the best of the authors' knowledge, no studies have explored the relationship between spirituality and substance use in a rural sample of largely Hispanic and Native American adolescents. This article reports on a study that examined the relationship between spirituality and religious participation and substance use in a multicultural sample of rural youths. THEORETICAL EXPLANATIONS FOR SUBSTANCE USE Risk Factors Among a number of theories that have been advanced to explain substance use among adolescents, two of the more prominent are peer influence and self-rejection or derogation. Peer groups can provide an environment in which substances are available, youths learn how to use substances, and a shared sense of identity in terms of attitudes, beliefs, and values emerges that re-enforces their use (Cowdery, Fitzhugh, & Wang, 1997; Menon, Barrett, & Simpson, 1990). Schools, in particular, offer a fertile environment for such associations to form. For example, school-related problems may increase associations with deviant peers, which in turn can foster substance use. Self-rejection or derogation also have been proposed as a framework for understanding substance use among adolescents (Warheit et al., 1995). This perspective emphasizes low self-esteem, rather than environmental factors, as the primary causal factor underlying substance use. Feelings of self-rejection and derogation, which may be heightened among Hispanic and Native American youths as a result of their ethnic minority status and mainstream oppression (Carrasquillo, 1991; Wright, 1994), may foster a cognitive-emotional status that facilitates substance use (Warheit et al. …