Background Stem cell transplantations from related or unrelated donors are used to cure leukaemia and other blood diseases. When a patient dies after an unsuccessful transplantation, interested unrelated donors are informed about the failure by their donor centre. Studies focussing on failed related donations show that donors undergo an intense grieving process. As there are only two investigations about reactions from unrelated donors, knowledge about their reactions is less comprehensive. Methods We conducted a prospective study of reactions of unrelated donors to the information of failed transplantations, subject to various communication methods (letter, phone). Questionnaires were sent to 395 unrelated donors who received the news of their recipients' deaths between November 2005 and August 2006. In addition, twelve in-depth interviews with selected donors were carried out. Results Unrelated donors were emotionally affected by the recipients' deaths, and it is appropriate to speak about a "Donor Grief" phenomenon, as the results of 325 returned questionnaires (return rate 82.3%) and in-depth interviews show. Donors demonstrated a range of feelings such as sadness, disappointment, grief, and helplessness. These feelings were often unexpectedly intense given the fact that the recipient was a stranger. Although the news caused grief, donors underlined that they nevertheless wanted to be informed. They preferred knowledge of the failure to uncertainty. The method of providing the information is only of secondary importance. Most donors favoured the way of communication they had experienced. Conclusion This result indicates that both phone and letter communication can be justified. However, phone communication seems to be superior with respect to aspects of sensitivity. In spite of transplantation failure and the associated negative feelings, most donors were happy to have donated and would be willing to do so again. Our results underline the special responsibility of donor centres for informing and supporting unrelated volunteer donors in case their recipients have died.