We examined the salience of multiple ecological factors (individual, family, peer, school, and community) as differential predictors of smoking for adolescent African-Americans and Whites in a sample of 2,029 7th-12th grade girls from a Mid-Atlantic southeastern state. Hierarchical regression analyses revealed that significant predictors of smoking in the White female model included coping by taking drugs, grades, frequency of using alcohol, frequency of using marijuana, parent quality, and perceived availability of cigarettes. Significant predictors of smoking in the African-American female model included coping by taking drugs, attempted suicide, frequency of alcohol use, frequency of marijuana use, hours spent in club activities, hours spent in sports, and socioeconomic status. Implications for prevention and intervention programs are discussed.