Background/Aims: The aims of this study were to examine the in vitro effects of IFN (interferon)-γ on growth of human stomach cancer cell lines and to investigate the antiproliferative effects of IFNγby cell cycle regulation. Methods: Three human gastric cancer cell lines, SNU-1, SNU-16 and AGS, and recombinant human IFN-γwere used. The cells were treated with IFN-γfor various time frames and/or at various concentrations and then, DNA synthesis, cell cycle and the expression of cel cycle regulators were examined. Results: IFN-γinhibited the proliferation of SNU-1 and SNU-16 in time- and concentration- dependent manners as judged by [3H]-thymidine incorporation assay. In the cell cycle analysis of SNU-1 and SNU-16, IFN-γinduced G1 block at the cell cycle. IFN-γincreased the expression of two or all three of the cycline-dependent kinase (CDK) inhibitors p21WAF1, p27Kip1, and p16INK4, depending on the cell line. Conclusions: These data suggest that the antiproliferative effect of IFN-γon human stomach cancer cell lines was mediated by increase in the expression of CDK inhibitors and blocking cell cycle at G1-S transition. (Kor J Gastroentero)1999;33:38 - 50)