The value of the social sciences is increasingly recognised in health services and clinical research, contributing to an increasing number of multi-disciplinary, multi-method studies. Such studies offer numerous advantages, but also pose particular challenges, including different approaches to or foci in research ethics across disciplines. Drawing on two similar studies conducted in coastal Kenya and in rural South Africa, we share the ethical challenges we faced in relation to several key principles, the responses we adopted, and the new dilemmas that resulted from our actions. Given that multi-disciplinary, multi-method studies are often reviewed by committees with greater familiarity with biomedical than social science research, we conclude by drawing on our experiences, and the wider literature and guidelines around conducting social science research, to make suggestions of additional considerations for social science elements of multi-disciplinary research. We also emphasise that in practice it is the social relationships that are established between researchers and field-teams, and between field-teams and community members, that are critical to fulfilling the moral (as opposed to the legal) aspects of ethics guidelines. These essential elements of ethical practice, and of producing quality data, are not easily tested and checked by ethics committees. Rather they are linked to the insight and integrity of the principle investigators and their research teams. Copyright © 2009 John Wiley & Sons, Ltd.