Transforming growth factor beta 1 (TGF-beta 1) has been shown to inhibit the function of various types of cells in vitro such as natural killer (NK) cells. However, this activity has not been well characterized in vivo. Therefore, twenty three patients with advanced gastric adenocarcinoma (AGC), with cytologically-proven malignant ascites, were evaluated in this study. We determined whether the NK activities of their lymphocytes from either peripheral blood or ascites were suppressed by tumor cell TGF-beta 1 expression. We also examined whether NK activity was more suppressed in peripheral blood versus in ascites where tumor cell-derived TGF-beta 1 is potentially more locally concentrated. The expression of TGF-beta 1 mRNA was examined in the tumor cells from the ascitic fluid of the AGC patients. The NK activities of lymphocytes in peripheral blood and ascites were measured by the 4-hour 51Cr-release assay. We determined that eleven of twenty three patients had tumor cells expressing high levels of TGF-beta 1 mRNA. The NK activity in these eleven patients was significantly lower than the NK activity in peripheral blood and ascites from twelve patients with low TGF-beta 1 expression. In addition, the NK activity in malignant ascites was significantly lower than the activity in peripheral blood in these high TGF-beta 1-expressing cancer patients (p < 0.05). We also monitored survival time in these advanced gastric cancer patients. However, the patients with high expression of TGF-beta 1 showed a trend towards reduced survival although this was not statistically significant. The data in this study are consistent with observations in the previous experiments that showed inhibitory effects of TGF-beta 1 on NK activities in vitro, we reported the same phenomenon in patients with advanced gastric cancer.