Based on a content analysis using framing theory, this article examines how the microbicide trials for HIV/AIDS prevention were portrayed in local newspapers in South Africa. Twenty-nine newspaper articles on microbicide research in South Africa appeared between 2004 and 2007 in 8 major South African newspapers; 13 had extended discussions of the microbicide trials while the remainder only mentioned them in passing. Six major topics were identified in these articles: participants; consequences of microbicide use; quality of the research design; research ethics; the stopping process (i.e. the way in which the microbicide trials were halted); and "villains" and "heroes." These topics were then inductively related to three emergent categories, named by the researchers as the: malicious microbicide trial, which characterizes the trials in highly negative, and disapproving ways; the marvelous microbicide trial, which frames the trials in highly positive and approving ways; and finally the multifaceted microbicide trial, which attempts to shed light on the complexities of the issues, rather than portraying them in one-sided terms. The report concludes with a discussion of the implications of the different media portrayals for public health in South Africa.