To the Editor: We thank Dr. Friel for his kind introductory remarks regarding our review article “Antioxidants as Therapy in the Newborn: Some Words of Caution”(1), and take no great issue with his other comments. As reflected in the title of our review, our intent was to introduce a note of caution, not prohibition. Our laboratory has a long history of studying antioxidant interventions in animal and cell culture models, with the ultimate hope that the collective data and advances from such models will allow that “leap of faith” to studies in human infants. Indeed, as Dr. Friel has pointed out, several groups have already taken such a leap. It was just this increase in human studies of antioxidants that stimulated us to write our review. We believed, rightly or wrongly, that there was a widespread, if understandable, lack of awareness by physicians of the important physiological roles played by reactive oxygen species, and the potential consequences of antioxidant interventions. One could equally posit that there is an equivalent lack of awareness of the capacity of many antioxidants to act as pro-oxidants. This is not to say that clinical trials of antioxidants should not happen: they should. They should not, however, happen without the investigators involved being as fully informed as possible of potential adverse affects.