An in vitro clonogenic assay was used to study the activity of 3 established cytotoxic drugs and 3 experimental agents against a series of 33 human transitional cell carcinomas. Strict adherence to rigid colony size criteria gave very reproducible results with the 3 cytotoxic drugs (adriamycin, mitomycin C and thiotepa) and our sensitivity curves are of the form expected on the basis of past experience with tumour cell lines. The unexplained plateau form curves which have previously led to criticism of the assay were not seen. Resistant subpopulations were found only in poorly differentiated tumours. This modified assay was then used to test 3 experimental agents for activity against transitional cell carcinoma. Sulphopentosan, DMSO and retinoic acid all proved inactive in this system.