Although 50% of all new global HIV infections occur among young people, our knowledge to date of the impact of adolescent HIV prevention interventions in developing country settings is limited. During 1999, a national HIV prevention programme for youth, called loveLife, was launched in South Africa. This paper describes the challenges faced in trying to evaluate such a national programme and the types of evidence that could be used to better understand the effect of programmes of national scale. A range of methods were planned to evaluate the programme, including national household surveys and programme monitoring data. Given the urgent need to scale-up programmes in an effort to reduce new HIV infections, a range of evidence should be assessed to measure the effect of large-scale, complex behavioural interventions as an alternative to randomised controlled trials.