It is well known that the central giant cell lesion (granuloma) of the jaws has a distinct female predilection. In addition, occasional cases of central giant cell lesion have been reported to have undergone marked proliferation in pregnant patients and in those undergoing hormonal therapy. As such, we have evaluated 10 central giant cell lesions for the detection of estrogen and progesterone receptor proteins with the use of immunoperoxidase staining. Surprisingly, however, immunostaining for estrogen receptor protein was essentially negative in all cases examined. Although an occasional mononuclear cell stained weakly positive for estrogen receptor protein, these findings suggest that in most cases, factors other than a direct influence of the ovarian hormones, estrogen and progesterone, are responsible for the development and growth of these lesions.