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The effects of ovarian hormones on the synthesis of ₂-macroglobulin in response to injury were investigated. After injection of turpentine to provoke synthesis of ₂-macroglobulin, the mean concentrations of this protein in serum were lower in intact female than in male rats. Sera from injured ovariectomized rats contained levels of ₂-macroglobulin similar to those of injured male animals. Administration to ovariectomized animals of oestradiol or oestradiol plus progesterone substantially reduced the levels of ₂-macroglobulin produced in response to injury. Administration of progesterone only resulted in a small increase in the response of ovariectomized animals to injury. Oestradiol and progesterone had no effect on the response of male rats to injury. These findings suggest that only in the female rat can these steroid hormones, especially oestradiol, regulate the synthesis of ₂-macroglobulin in response to tissue injury.