Familiarity (i.e., relationship closeness) and relationship quality (i.e., the degree of negativity/positivity) have been suggested as critical components, affecting stigmatizing attitudes toward those with mental illnesses. The present study experimentally tested components of, and expanded upon, a recent theoretical framework by P. W. Corrigan and Nieweglowski (2019), which proposes a convex (u-shaped) curvilinear relationship between familiarity and stigma (i.e., people hold the most stigma toward others at the lowest and highest levels of familiarity) rather than a linear one (i.e., stigma simply decreases as familiarity increases). By examining how both familiarity and relationship quality affect public stigma broadly, as well as microaggressions specifically, this research adds to the growing body of literature on mental illness stigma. Undergraduate students (N = 242) were randomly assigned to read one of six vignettes via a 2 (quality: positive vs. negative) × 3 (familiarity: coworker, cousin, romantic partner) between-subjects factorial design. Following, participants completed measures assessing stigmatizing attitudes and microaggression endorsement toward the vignette character. There was a significant main effect of relationship quality on stigmatizing attitudes only; on average, those in the three negative conditions had significantly higher stigmatizing attitudes than those in the positive conditions. Conversely, familiarity only had a significant main effect on microaggressions, wherein higher familiarity groups demonstrated higher microaggression endorsement. No significant interactions were found for either variable. These results suggest that stigmatizing attitudes and microaggressions may be functionally different, and further research is required to clarify current theoretical frameworks in understanding how relational contexts impact these negative attitudes.