Human transitional cell carcinoma was successfully grown in short-term tissue culture in 17 of 29 specimens collected (58 per cent). Morphologic parameters of the explants were studied with light and transmission electron microscopy before and after incubation with either thiotepa or 5-fluorouracil. Thiotepa was found to produce marked acantholysis in 43 per cent of those studied. We postulate that thiotepa acts primarily through breakdown of cell adherence. Changes found with 5-fluorouracil were primarily confined to the nucleus.