Why do some heterosexual people react in a negative manner when pondering or experiencing romantic or sexual overtures from persons of their same-sex, whereas other heterosexual people react more positively? To answer this question, this cross-sectional, correlational study examined individual difference predictors of heterosexual people’s responses to romantic or sexual overtures from same-sex persons. Our sample comprised 306 men and 307 women, ages 18–35 years, who were recruited from Mechanical Turk and identified as cisgender and heterosexual. Our hypotheses were premised on the theoretical construct of reactive group distinctiveness. Specifically, we explored predictors of heterosexual individuals’ negative perceptions of same-sex overtures. We found that more negative reactions to same-sex overtures were uniquely predicted by old-fashioned sexual prejudice, modern sexual prejudice, and desire to be perceived as gender conforming, via the mediators of social distance from same-sex sexual minority individuals and desire to be perceived as heterosexual. Gender moderated these relationships inconsistently. These findings indicate that two classes of individual differences—sexual prejudice and gender conforming reputation desire—are uniquely associated with heterosexual persons’ reactions to overtures from same-sex persons. We explain how these findings evidence the process of reactive group distinctiveness.