We observed immediate-type hypersensitivity reactions in 6 of 600 donors who underwent automated plateletpheresis procedures. Ethylene oxide gas, which was used to sterilize plastic components in the disposable apheresis kits, represented a possible source of sensitization. In skin-prick testing, 4 of the 6 donors who had had a hypersensitivity reaction and none of 40 controls who had not had such a reaction had positive tests when an ethylene oxide-human serum albumin reagent was used (P less than 0.001). Radioallergosorbent testing revealed that serum from 4 of the 6 donors who had reactions, but from only 1 of 145 controls, contained IgE antibodies to ethylene oxide-albumin (P less than 0.001). All six of the donors who had reactions had specific ethylene oxide-induced basophil histamine release (mean release [+/- SE], 34.2 +/- 5.6 percent), whereas none of four controls had specific histamine release in response to ethylene oxide (mean release, 5.7 +/- 1.2 percent; P less than 0.005). Repeat plateletpheresis in five of the donors who reacted was accompanied by a recurrence of mild allergic symptoms. These studies demonstrate that sensitization to ethylene oxide gas can occur in healthy plateletpheresis donors and that it may result in immediate hypersensitivity reactions during the donation. The prevalence of such reactions was 1.0 percent in our apheresis donor population.