Epidermal growth factor (EGF), a potent mitogen and tumor promoter, is excreted in urine permitting it to incubate with urothelial cells. We have previously shown that the distribution of receptors for EGF (EGF-Rs) on malignant urothelium changes to favor contact between EGF-Rs and intraluminal EGF. OBJECTIVES. To determine if concentrations of EGF in voided urine are different in patients with transitional cell carcinoma (TCC) of the bladder than in those without this condition. METHODS. EGF was measured by radioimmunoassay in the urine of 54 patients with newly diagnosed TCC (16 with grade 1, Stage Ta lesions, and 38 with grade 3, Stage T > or = 2 lesions) and 66 pathologic and normal controls without TCC. Subjects were matched for age and good renal function. RESULTS. EGF concentrations were significantly reduced in patients with TCC compared with controls either when uncorrected (p < 0.0001) or corrected (p < 0.000000002) for urinary creatinine excretion. CONCLUSIONS. The reduced concentration of EGF in voided urine supports previous evidence that the urinary EGF/urothelial EGF-R interaction is important for TCC development and growth, and has the potential to serve as a marker of tumor persistence, recurrence, and therapeutic response.