Debates on the role of scientific knowledge to affect behaviour are continuing. The theory of planned behaviour suggests that behaviour is influenced by attitudes, subjective norms and perceived behavioural control and not by knowledge. However, a large body of knowledge argues that increased HIV/AIDS-related knowledge leads to the adoption of safe behavioural practices. The purpose of this non-experimental survey study, therefore, was to investigate the correlation between academic HIV/AIDS knowledge, functional HIV/AIDS knowledge and self-reported behavioural preferences of 300 biology and 243 non-biology students from nine South African schools. Results suggest a correlation between students' understanding of academic and functional HIV/AIDS knowledge. The behavioural preferences of both biology and non-biology students were generally the same and safe. Among biology students, correlation was observed between academic HIV/AIDS knowledge and self-reported safe behavioural preferences, which was not the case for non-biology students, where functional HIV/AIDS knowledge correlated with self-reported safe behavioural preferences. Within schools, however, no correlation was found between both forms of HIV/AIDS knowledge and self-reported safe behavioural preferences. There were indications that context-specific local factors have a greater influence on behavioural preferences. These findings suggest that the type of knowledge that could influence behaviour is informed by context-specific dynamics.