A monoclonal antibody directed against sialylated LewisX (SLEX) was tested with the serum of 615 cancer patients, 166 patients with non-malignant diseases, and 136 normal persons. The SLEX antibody reacted with the sera of the cancer patients in the following percentages: 29% lung, 19% breast, 12% ovary, 25% colorectal, 13% head and neck, and 13% miscellaneous. SLEX was positive for 22% of stages III and IV (late-stage) cancers as compared with 5% early-stage tumors. Among 80 patients with adenocarcinoma of the lung in the late stages, 45% were positive for SLEX. However, among 54 patients having squamous-cell lung cancer in the late stages, 15% were positive. In 25 cases of small-cell lung cancer, 24% were positive. Among patients who had measurable lung cancer, 4/7 with adenocarcinoma over 3 cm in diameter were positive whereas 0/16 patients with tumors under 3 cm were positive. Four patients who had tumor regression showed a more than 50% decrease in SLEX values whereas in 7 patients with progressive tumors, a more than 50% increase in SLEX levels was found. When tested simultaneously with CEA, SLEX produced positive reactions with the sera of some patients who were negative for CEA. The reaction pattern was distinct, indicating that another antigen was being detected. When used in combination, the percentage of sera that were positive increased. We conclude that the use of SLEX is useful for monitoring of cancer patients.