On the basis of critical discussions which have taken place in recent years in the Federal Republic of Germany, certain methodological, ethical and legal problems arising in relation to controlled trials are discussed. Because of methodological inconsistencies inherent in the experimental approach, the efficacy of a drug must in any case be judged by physicians. This leads to major ethical and even--at least in Germany--legal problems which impose considerable limits on the feasibility of controlled trials in Germany. Editor's note: This paper is written at the invitation of the journal, following the considerable controversy on the ethics of clinical trials in the European Journal of Clinical Pharmacology (8-11). A critical commentary follows the paper with a short response from the authors and a further response from the commentator.