Monoclonal antibodies (Mabs) to human tumor antigens have potential for tumor detection and treatment. For bladder carcinoma, the detection of exfoliated tumor cells in urinary specimens may be accomplished with Mabs reacting to tumor cell-surface components. This method may be useful for screening and monitoring carcinogen-exposed workers. A Mab generated by our laboratory, 3G2-C6, reacts with high affinity to a cell-surface component expressed by bladder tumor cells. The potential utility of this Mab in detecting exfoliated tumor cells was evaluated in bladder wash specimens. The Mab method detected positive cells in 87% (56/64) of specimens from patients with bladder cancer, including a great majority with grade 1 tumor and carcinoma in situ, superior to the routine cytology done on the same specimens. Cells in specimens from patients with urinary calculi, chronic cystitis, and history of bladder cancer also reacted with the Mab, suggesting that other stimuli can induce antigen expression. The Mab method can also be performed on urine samples, thus allowing evaluation of the ability of the Mab to identify premalignant, malignant, and other abnormal exfoliated cells in urine. The Mab method represents a unique opportunity to develop noninvasive detection of bladder cancer and to monitor and screen bladder cancer high-risk groups.