Results of the study suggest that American Indian female adolescents may be at greater risk for drug use than boys because they reported receiving significantly more drug offers and indicated more difficulty in refusing drug offers than boys. Consistent with a 2002 ecodevelopmental theory, it seems that social and familial relationships influence the number of drug offers given to American Indian youth. However, the results indicate a disparity of experiences for female and male American Indian adolescents regarding their exposure to drug offers and the degree of perceived difficulty in handling such offers. This suggests that social and familial relationships may affect girls and boys differently. It is recommended that future research explore other culture-specific and gender-specific aspects of drug use risk and resiliency with this understudied population of adolescents. To date, much of the research on gender differences in adolescent drug use has focused on Caucasian youth, and of the few studies that have examined females of different ethnic groups, samples have typically been limited to comparisons between Caucasian, African-American, and Hispanic girls. The intent of this study was to examine the gender differences in patterns of drug offers among a sample of 71 American Indian middle school students. The study begins with a literature review. It continues by analyzing the salient environmental characteristics in relation to substance-using behaviors for females and males. Lastly, a discussion is presented on the way in which the findings contribute to the understanding of gender-specific, ecological correlates related to drug offers for American Indian youth practices for these youth. Tables, references