Platelet transfusions from RhD-positive (D-positive) donors are often given to RhD-negative (D-negative) cancer patients. The low observed rate of alloimmunization has been attributed to disease and therapy-related immunosuppression. We have studied the occurrence of alloimmunization in 16 D-negative patients who did not have detectable anti-D prior to autologous bone marrow transplantation for malignant disease. All received D-positive platelets, but no other D-positive blood product. Three patients (19%) developed anti-D at 13, 24 and 83 days, respectively, after first receiving D-positive platelets, and after a total dose of 53, 65 and 119 D-positive platelet unit equivalents, respectively. Two of them also developed anti-C. The 13 patients in whom anti-D was not detected were also heavily transfused with D-positive platelets (mean +/- SD = 136 +/- 82 platelet unit equivalents). In 6 of them, the last recorded antibody screen was less than 3 months after the first D-positive platelets, and may not exclude a primary immune response. Thus, despite profound immunosuppression associated with autologous marrow transplantation, alloimmune responses to D-positive red cells in platelet concentrates can occur in some D-negative recipients.