A positive cross-match in cadaveric liver transplantation is relatively acceptable, but its role in living donor liver transplantation (LDLT) is less well known. The aim of this study is to examine the significance of cytotoxic crossmatch in adult-to-adult LDLT using small-for-size grafts. Forty-three adult-to-adult LDLTs were performed at Seoul National University Hospital (Seoul, Korea) from January 1999 to July 2001. Subjects consisted of 27 men and 16 women with an average age of 45.4 years. Average liver graft weight was 565.3 ؎ 145.7 g, and average graftrecipient weight ratio (GRWR) was 0.89% ؎ 0.20%. HLA cross-match testing by lymphocytotoxicity and flow cytometry was performed routinely preoperatively. Factors that may influence survival, such as age; sex; blood group type A, type B, type O compatibility; cytotoxic cross-match; donor age; surgical time; cold ischemic time; and GRWR, were analyzed. Nine patients (20.9%) died in the hospital. There was a greater in-hospital mortality rate in women than men (37.5% v 11.1%; P ؍ .049). The extra-small-graft group (0.54% < GRWR < 0.8%; n ؍ 14) showed greater in-hospital mortality rates than the small-graft group (0.8% < GRWR < 1.42%; n ؍ 29; 42.9% v 10.3%; P ؍ .022). A positive cross-match was detected in 4 women transplant recipients, and 3 of these patients belonged to the extra-small-graft group. All patients with a positive cross-match died of multiorgan failure after early postoperative acute rejection episodes. Positive cross-match was the only significant factor in multivariate analysis (P ؍ .035). In conclusion, when lymphocytotoxic cross-match and flow cytometry are significantly positive, adult-to-adult LDLT using small-forsize grafts should not be performed. (Liver Transpl 2002; 8:1109-1113.)