South Africa retains the highest HIV prevalence in the world, with the incidence of infection growing fastest among youth. The purpose of this investigation was to inform preventive family-based interventions designed to reduce youth HIV risks. In 2009, 38 black South African caregivers and youth (ages 10-14) participated in key informant interviews and focus groups, which were coded for themes related to family communication about sex. Findings highlighted a cultural taboo against communication that among some caregivers was shifting. Informed by this qualitative data, in 2010, 97 black South African caregivers and 97 youth (ages 10-14) completed measures designed for quantitative comparisons between the caregiver and youth generations. Results were that youth reported significantly more communication about sex topics than did their caregivers, and significantly lower perceptions of caregiver responsiveness to communication than their caregiver’s self-report. Importantly, although youth reported that they would prefer to ask their mother first a question about sex, currently few do so. Male youth and their caregivers were significantly less likely to report communication about sex topics than were female youth and their caregivers. Correlations indicated that youth-reported perceptions of their caregivers’ responsiveness are likely one of the best indicators of whether and how communication occurs, and that being a younger caregiver is associated with higher self-reported caregiver responsiveness. Regarding safety, nearly twice as many caregivers reported feeling that their neighborhood was “not safe” than did youth and the majority of caregivers reported talking to their youth about sexual violence.