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This paper presents the rationale, development and application of "Unplugged', a new school programme for the prevention of substance abuse, which is based on the comprehensive social influence approach (CSI). The programme was developed, implemented and evaluated by a cross-disciplinary group of experts in the frame of a multi-centre study in seven European countries. The basic curriculum consists of 12 units, which are delivered by class teachers to a target population of 12-14 year-old students. Additional programme components were workshops for the students' parents and debriefing sessions led by class peers. The programme's application was monitored by means of structured report forms. This process monitoring allowed for the analysis of problems in implementation, as well as of participatory aspects. "Unplugged" is the first comprehensive social influence school curriculum in Europe of which the efficacy has been evaluated in a field trial, and it also constitutes an example of a theory- and evidence-based programme against youths' substance use. This report can provide public health and school decision makers with tools to make an informed choice on these kinds of programmes and to survey their application. (Contains 2 figures, 4 tables and 1 note.)