The majority of epithelial ovarian cancers originate in the ovarian surface epithelium. The ovarian surface epithelium is a hormonally responsive tissue, and hormones are thought to play a key role in the development of this type of cancer. Gonadotrophin releasing hormone II is one of 2 isoforms which are thought to act through gonadotrophin releasing hormone receptor I, and gonadotrophin releasing hormone II has been shown to cause growth inhibition of cultured ovarian surface epithelium. The aim of this study was to investigate the expression levels and prognostic significance of gonadotrophin releasing hormone II and the gonadotrophin releasing hormone receptor I in epithelial ovarian cancer. Gonadotrophin releasing hormone II and gonadotrophin releasing hormone receptor I messenger RNA expression was examined in 23 cancers and 7 normal ovarian surface epithelium samples by quantitative real time polymerase chain reaction. An ovarian cancer tissue microarray containing 139 cases was constructed and immunohistochemical analysis of gonadotrophin releasing hormone II and gonadotrophin releasing hormone receptor I protein expression was performed and correlated with clinical outcome data. Gonadotrophin releasing hormone II messenger RNA expression was lower in cancer samples compared to normal ovarian surface epithelium samples (P < .05). Gonadotrophin releasing hormone II protein expression correlated with histologic subtype (25% serous versus 45% nonserous, P < .05) but not with overall survival. Gonadotrophin releasing hormone receptor I messenger RNA expression was highest in serous tumors when compared to non serous (P < .05) and normal tissue (P < .001). Expression of the gonadotrophin releasing hormone receptor I protein was also found to correlate with patient survival (P < .05). We have demonstrated gonadotrophin releasing hormone II and its receptor, gonadotrophin releasing hormone receptor I, are present in clinical ovarian samples, and that gonadotrophin releasing hormone receptor I protein expression is a favorable prognostic factor, suggesting these proteins play an important role in the development of epithelial ovarian cancer.