In the present study, the Anxiety Sensitivity Index [ASI; Behav. Res. Ther. 24 (1986) 1] was administered to 282 American Indian and Alaska Native college students in a preliminary effort to: (a) evaluate the factor structure and internal consistency of the ASI in a sample of Native Americans; (b) examine whether this group would report greater levels of anxiety sensitivity and gender and age-matched college students from the majority (Caucasian) culture lesser such levels; and (c) explore whether gender differences in anxiety sensitivity dimensions varied by cultural group (Native American vs. Caucasian). Consistent with existing research, results of this investigation indicated that, among Native peoples, the ASI and its subscales had high levels of internal consistency, and a factor structure consisting of three lower-order factors (i.e. Physical, Psychological, and Social Concerns) that all loaded on a single higher-order (global Anxiety Sensitivity) factor. We also found that these Native American college students reported significantly greater overall ASI scores as well as greater levels of Psychological and Social Concerns relative to counterparts from the majority (Caucasian) culture. There were no significant differences detected for ASI physical threat concerns. In regard to gender, we found significant differences between males and females in terms of total and Physical Threat ASI scores, with females reporting greater levels, and males lesser levels, of overall anxiety sensitivity and greater fear of physical sensations; no significant differences emerged between genders for the ASI Psychological and Social Concerns dimensions. These gender differences did not vary by cultural group, indicating they were evident among Caucasian and Native Americans alike. We discuss the results of this investigation in relation to the assessment of anxiety sensitivity in American Indians and Alaska Natives, and offer directions for future research with the ASI in Native peoples.