OBJECTIVE Approximately 5.6 million South Africans are living with human immunodeficiency virus (HIV; UNAIDS, 2010). Prevalence among Black adolescents and young adults is particularly alarming. This pilot study of an HIV preventive intervention targeting South African youth contributes to the growing body of research on culturally competent family-based interventions. METHODS A total of 99 parent-child dyads were enrolled in an experimental repeated measures study, using a wait-list control group. Our 6-session intervention targeted general parenting (relationship quality, parental monitoring, and involvement), gender roles, and parent-youth communication about sex (content and quality). Parents and youth were assessed at baseline, postintervention, and 6-month follow-up. Eligibility included being the primary female caregiver of a 10- to 14-year-old child with whom they spent at least 4 nights a week and being able to participate in English or Xhosa. RESULTS Effect sizes with this small sample met or exceeded those of other family-based HIV interventions for youth in the United States and South Africa (e.g., Bell et al., 2008; Forehand et al., 2007). Parents' reports at postintervention indicated larger effect sizes for general parenting than youths' reports indicated. Parents' reports showed medium to large effects for all sex communication outcomes at postintervention and the 6-month follow-up. Youth reports demonstrated small to medium effects for most communication variables and these effects lasted through the 6-month follow-up period. CONCLUSIONS Intergenerational social networks (e.g., families) hold promise for HIV prevention among South African youth. A full efficacy trial with longer-term follow-up and attention to maintenance of effects is warranted.