We recently showed that the levels of secreted human leukocyte antigen-G (HLA -G), a nonclassical MHC class I antigen, are significantly elevated in malignan t effusions in ovarian carcinoma compared to benign ones. The objective of this study was to evaluate the expression and clinical role of HLA-G in effusions an d corresponding solid tumors from patients diagnosed with advanced-stage ovaria n carcinoma. Effusions (=148), corresponding primary tumors (=66), and metastati c lesions (=122) were analyzed using immunohistochemistry with an anti-HLA-G m onoclonal antibody. HLA-G was detected in cancer cells in 49/148 (33%) effusio ns, 33/66 (50%) primary tumors, and 59/122 (48%) solid metastases. These diffe rences did not reach statistical significance. Expression in effusions and solid metastases significantly correlated (P = 0.029). HLA-G expression in tumor cel ls was significantly lower in effusions obtained during or following chemotherap y (P = 0.038). The presence of HLA-G-positive tumor cells in effusions obtaine d prior to the institution of chemotherapy correlated with better overall surviv al (P = 0.042). HLA-G expression in primary tumors and solid metastases did not correlate with any of the clinicopathologic parameters studied. HLA-G is expre ssed in a significant number of ovarian carcinomas at all anatomic sites. The re duced expression of HLA-G in post-chemotherapy effusions and its correlation w ith improved survival may be related to preferential susceptibility of HLA-G-e xpressing cells at this site. Our findings suggest a new role for HLA-G as a pr ognostic indicator in advanced-stage ovarian cancer in effusions. We recently showed that the levels of secreted human leukocyte antigen-G (HLA-G), a nonclassical MHC class I antigen, are significantly elevated in malignan t effusions in ovarian carcinoma compared to benign ones. The objective of this study was to evaluate the expression and clinical role of HLA-G in effusions an d corresponding solid tumors from patients diagnosed with advanced-stage ovaria n carcinoma. Effusions (= 148), corresponding primary tumors (= 66), and metastati c lesions using immunohistochemistry with an anti-HLA-G moclonal antibody. HLA-G was detected in cancer cells in 49/148 (33%) effusio ns, 33/66 (50%) primary tumors, and 59/122 HLA-G expression in tumor cel ls was significantly lower than effusions obtained during or following the chemotherap y (P = 0.038) The presence of HLA-G-positi ve tumor cells in effusions obtaine d prior to the institution of chemotherapy correlated with better overall surviv al (P = 0.042). HLA-G expression in primary tumors and solid metastases did not correlate with any of the clinicopathologic parameters studied. HLA-G is expre ssed in a significant number of ovarian carcinomas at all anatomic sites. The re duced expression of HLA-G in post-chemotherapy effusions and its correlation w ith improved survival may be related to preferential susceptibility of HLA-Ge xpressing cells at this site. Our findings suggest a new role for HLA-G as a prognostic indicator in advanced-stage ovarian cancer in effusions.