Catalytic activity and FdUMP binding characteristics of thymidylate synthase (TS) were determined in 22 tumor biopsies of patients to be treated (15) or just treated (7) for colorectal cancer with 5-fluorouracil and leucovorin. In 19 samples both parameters could be determined and were found to represent a wide range (15-20 fold). High values of activity correlated with no response, but low values of binding or activity were found in responders as well as in non-responders. It is concluded that the determination of parameters related to TS function is feasible in tumor biopsies and its relevance for clinical management deserves further study.