A human gastric signet ring cancer cell line (Mz-Sto-1) was established in tissue culture from the ascites fluid of a 54-year-old patient. The tumor cells growing in tissue culture exhibit the morphological characteristics of signet ring cells in phase contrast and transmission electron microscopy. Mz-Sto-1 cells grow as monolayer with a population doubling time of 28-36 hr during exponential growth phase and show a chromosome number between 72 and 74. In the cellular DNA of Mz-Sto-1 cells no amplification of 19 oncogenes studied is observed, c-myc included. Mz-Sto-1 cells secrete 150-250 ng CEA per 10(7) cell in 3 days, but no AFP. In addition Mz-Sto-1 cells and 2 already established gastric cancer cell lines MKN-28 and MKN-45 express HLA- and blood group related antigens (A, Lewis). HLA-DR antigens, which are regularly detected on normal stomach epithelium, are not found on any of the 3 cultured gastric cell lines. Mz-Sto-1 cells represent the first human gastric cancer cell characterized ultrastructurally as signet ring cells. This line will be a valuable tool to study the biology and genetics of gastric carcinoma, to test cytostatic drugs and to define new antigenic markers for stomach cancer.