Medical students encountering patients with unfamiliar, unconventional sexual practices may have attitudes that can affect open communication during sexual history-taking. We measured changes in first-year US medical student attitudes toward 22 non-traditional sexual behaviors before and after exposure to human sexuality instruction. An electronic, hand-held audience response system was used in a lecture hall to sample anonymous student attitudes toward this sensitive topic. Several attitudes were influenced by instruction, as shown by statistical comparisons before and after instruction. Students' attitudes shifted toward patterns favoring treatment for five out of 10 paraphilias that are not harmful of others. Most students favored imprisonment for pederasty before instruction, consistent with lessons about mandatory reporting of child sexual abuse, and this attitude increased non-significantly after instruction. Student attitudes were generally accepting of homosexuality, but were more accepting of female than male homosexuality, both before and after instruction. Implications of these diverse effects of our lecture-based curriculum on attitudes toward non-traditional human sexual behavior are discussed, as well as benefits of audience response systems in anonymously assessing students' attitudes toward sensitive topics. (Contains 2 figures and 1 note.)