In 1998, Baxter Healthcare announced that it was abandoning its product, diaspirin–crosslinked hemoglobin (DCLHb), the first ‘blood substitute’ to complete all phases of human trials. The company announced that the phase III (pivotal) trials in humans had resulted in an unexpectedly high survival in a group of patients serving as controls for those who received their product in a trauma setting. It is not possible to quantitate the time, efforts and money that were expended in the course of developing this product, from 1985 to 1998. It is rumored that the giant healthcare company had expended more than a half billion dollars on this product, not to mention the investment in the same product by the US Army, the National Institutes of Health and many independent university–based scientists. The disappointment was profound and far–reaching. Although the threat of HIV transmission by banked blood has all but disappeared in the developed world, still the bulk of the world’s population faces blood shortages, which this product and its future generations might have helped alleviate. Only Baxter and the Food and Drug Administration may forever know key elements of the history of development of this product. However, because the US Army decided to make its version of the product widely available to scientists, there is a substantial published record, contributed to by both Baxter and independent scientists. Examination of this record leads to the conclusion that there is no single reason for failure. However, it shows that the characteristic hemodynamic response caused by ααHb increased vascular resistance, and probably eliminates its potential as a red cell substitute. Newer solutions that overcome this limitation should fare better in clinical development when this problem is overcome.