Gonadotropin-releasing hormone and its receptors have been identified in several human malignancies. We evaluated gonadotropin-releasing hormone receptor expression in 30 primary and recurrent endometrial stromal sarcomas. Archival formalin-fixed and paraffin-embedded material was analyzed immunohistochemically with antisera to gonadotropin-releasing hormone receptor type I and gonadotropin-releasing hormone receptor type II using the peroxidase-antiperoxidase method. Gonadotropin-releasing hormone receptor types I and II were demonstrated in most primary endometrial stromal sarcomas in varying intensity and percentage (range, 10-100%). The staining pattern was either diffuse cytoplasmic or granular/vesicular in perinuclear distribution. Recurrences stained stronger than primary tumors. The demonstration of gonadotropin-releasing hormone receptors I and II expression in endometrial stromal sarcomas may be a rationale for a clinical study of gonadotropin-releasing hormone analogs in the treatment of women with endometrial stromal sarcomas.