Cultural sensitivity is increasingly recognized as a means to enhance the effectiveness of health promotion programmes all over the world. Sociocultural meanings and terminology of diseases are important in understanding how different groups perceive and interpret illness. This study was conducted as part of the process of developing and adapting a sexually transmitted infection (STI)/HIV peer led health education intervention for soon-to-be-released inmates who were predominantly Nguni speakers in South Africa. Two focus group discussions (FGDs) were conducted with prison inmates in each of four facilities. Additionally, one FGD was conducted in each prison with non-health trained (custodial) personnel who were Nguni speakers from the same community (n = 27). The data revealed unique terminology and meanings attached to several biomedically defined STIs. These sociocultural constructions were not limited to inmates as findings from warders' discussions showed a similar pattern. Moreover, we found the existence of a number of traditional 'folk' STIs and culture-specific prevention methods. These conceptualizations influence reported health-care-seeking behaviour, where dual consultation of traditional healers and biomedical remedies is widely practiced. The research has biopsychological as well as cultural implications for the development and adaptation of contextually relevant health promotion interventions.