Psychological distress among college students represents a serious health concern. The aim of this research was to investigate, for the first time, whether interactions between rumination and different measures of stress could differentially predict components of psychological distress, within a diathesis-stress framework. This self-report study employed a longitudinal design, spanning a period of 6 months. One hundred sixty-one undergraduate college students completed selected measures of psychological distress, rumination, and stress at two time points 6 months apart. Both independent and interaction effects were examined through hierarchical regression analyses. Rumination and stress were found to interact significantly to predict the social dysfunction components of psychological distress. Other main effects are reported. The evidence supported the proposed diathesis-stress model and extended previous research by relating rumination to different components of psychological distress prospectively.