The present study seeks to identify factors among university students that may be associated with homophobic attitudes and whether homophobia may be reduced by educational interventions, such as knowledge-based curricula found in college sexuality courses. Participants were 128 undergraduate students attending a small, private university in the northwestern region of the United States. At the beginning and end of the fall semester 2004, survey packets consisting of a demographic questionnaire, the Sexual Opinion Survey, the Homophobia Scale, a sexual knowledge survey, and the Bem Sex Role Inventory were administered to students attending a human sexuality class and a comparison group of students enrolled in professional and social science introductory courses. Relative to the comparison group, homophobia levels significantly decreased over the course of the semester among students attending the sexuality class. The effect of attending the class on reducing homophobia was partially mediated by an increase in self-reported knowledge about sexual matters. Taken together, these results suggest that the knowledge-based curriculum of sexuality courses may play an important role in affecting broader attitudes about sexuality among college students, including attitudes about homosexuality. (Contains 3 tables.)