OBJECTIVES: The objective of the present study is to describe the compliance observed with a prescribed once a day placebo over a 28 days period in adolescent healthy volunteers, in school-dwelling youngsters in Belgium. METHODS: Eighty students were asked to take a placebo once a day during 28 days. Tablets supply was dispensed by sequences of 14 days either in an electronic pill box (MEMS®) or in an electronic blister pack (Cerepak®) according to a crossover design. Both devices allowed real time electronic compilation of dosing histories. At the end of the study, students were asked to assess their own compliance with a structured questionnaire. RESULTS: Compliance data were available for 78 students. We observed no difference in compliance between the two monitoring devices (p=0.682), nor between periods (p=0.462), and no carry-over effects (p=0.599). 46% of the students took most of their doses in the morning (before 10:00AM) and 49% in the evening (after 04:00PM). Compliance was higher (p=0.016) among the students who took their pills in the morning (92% vs 85%). Only 9 (11%) students took all of the 28 prescribed doses and 36 (46%) missed more then 5 doses. There was a strong weekend effect. The probability to take a tablet on a Friday or a Saturday was reduced by 30% (p<0.0001). Only 58% of the subjects were able to estimate reasonably well their compliance with the prescribed regimen. CONCLUSIONS: To be compliant with drug therapy is a burden for the majority of adolescents, most of whom are in good health and have little experience with taking medicines. Evening and weekend discipline seems to be problematic. No differences in compliance by measuring device were observed. When precise assessment of compliance is crucial for the interpretation of study results, electronic monitoring should be used, especially in adolescent populations.