Sialyltransferase activity was measured in plasma samples using desialated fetuin as the acceptor and cytidine 5'-phosphate-sialic acid as donor. The data show an increased enzyme level in 56 of 65 cancer patients studied, as compared with normal control values. The enzyme was not significantly elevated during lacation or in liver cirrhosis, but it was elevated in rheumtoid arthritis. Of the patients with cancer, 35 showed plasma enzyme levels above any value encountered in rheumatoid arthritis plasmas. The determinants of enzyme level in cancer appear to be complex: monitoring of plasma sialytransferase may be of value in measuring tumor progression, metatastatic involvement, or success of therapeutic programs.