This paper introduces a series of invited essays on current controversies in basic cancer research. The initial group of essays focuses on the detection and interpretation of molecular and cellular changes suspected to be of importance in the cause and pathogenesis of cancer. There are two formats: (i) differing viewpoints are presented in parallel, or (ii) the author(s) evaluate a hypothesis in light of available data. Each type of paper aims to critically evaluate current hypotheses and supporting data, while avoiding pronouncements on validity. Recent advances in molecular biology now permit us to consider genes as chemical entities. Individual genes can be isolated, cloned to produce multiple copies, sequenced, and assayed for biological function. This new molecular technology is being applied to fundamental questions in cancer research. The controversies resulting from these pioneering studies are the topics of the initial papers in this series. Forthcoming essays will concern the mechanism(s) of tumor promotion; a search for cancer genes by DNA transfection; the role of DNA rearrangements as initiating events in carcinogenesis; the O6position of guanine as a critical target of carcinogens; and metals as mutagens and carcinogens.