Eleven patients with recurrent superficial bladder tumours were treated with 6 weekly instillations of 10 million IU Introna and 1000 mg 5-fluorouracil for 1 h. Before and immediately after the first treatment biopsies were taken from normal urothelium and tumour for analysis of thymidylate synthase (TS). One papillary tumour was left as a marker. Tumour tissue had 9 times higher TS concentrations than normal urothelium (0.97 versus 0.11 pmol/g, p < 0.005). Despite a large variation in TS concentration in the tumours between different patients (range 0.02-2.24 pmol/g), after instillation the TS concentration decreased significantly in all but one patient. Six patients had complete and 2 had partial tumour regression after treatment. The effect was inversely correlated to the initial TS value. A low TS value seemed to predict a good response. The data suggest that weekly administrations are not sufficient in those with high TS concentrations. New treatment schedules may be beneficial in those with highly proliferating bladder tumours.