As with all early-stage testing of investigational drugs, clinical trials targeting HIV/AIDS can pose unknown risks to research subjects. Unlike sick participants seeking a therapeutic benefit, the motivations and barriers for healthy volunteers are more complex and understudied. Drawing on interviews and clinical trial data from 178 healthy volunteers, we examine how they perceive HIV/AIDS studies in the early stages of testing. A subset of healthy volunteers see Phase I HIV/AIDS studies as particularly risky for reasons ranging from fears of catching the disease to long-lasting and uncomfortable side effects or even inexplicable fears that they cannot articulate. Some participants have had past negative experiences in such trials that inform these views, but others cite information from staff and other participants as influential. Healthy volunteers’ general fears concerning AIDS also shape their views of participating in Phase I HIV/AIDS clinical trials.