We present results from life history interviews with 60 young adults from southern Uganda. Using a novel qualitative case-control design, we compared newly HIV-positive cases with HIV-negative controls matched on age, gender, marital status, and place of residence. Relationship context was the most salient theme differentiating cases from controls. Compared with HIV-negative respondents, recent seroconverters described relationships marked by poorer communication, greater suspicion and mistrust, and larger and more transitory sexual networks. Results highlight the importance of dyadic approaches to HIV and possibly of couple-based interventions. Using HIV-matched pairs allowed additional understanding of the factors influencing transmission. This hybrid methodological approach holds promise for future studies of sexual health.