Recent meta-analyses of HIV/AIDS health communication show that fear appeals have a negative effect on condom use. It has been argued that these negative effects may apply to certain behaviors (condom use) but not to others (e.g., sexual abstinence), and that these negative effects occur for Western cultures but not necessarily for African cultures. To assess whether the effects of fear appeals depend on the types of behavior recommended and on the cultural background of the target audience, information is needed on the existence of cultural differences with respect to the fear evoked by various consequences, as well as to the perceived effectiveness of various countermeasures. This study presents the results of a survey among 435 South African adolescents (age 12–19) who differ with respect to their cultural orientation, living circumstances, religion, etc. The results provide evidence for the presence of cultural differences with respect to evoked fear, response efficacy, and self-efficacy. Furthermore, the results provide a possible explanation why fear appeals often are ineffective within the context of communication about HIV/AIDS.