Monoclonal antibodies to the extracellular domain of the c-erbB-2 oncoprotein (p185) react with routinely processed, paraffin-embedded human tissues, and positive staining with these reagents has been shown to correlate with gene overexpression. To determine whether such antibodies would add prognostic data to the analysis of a pre-defined subset of transitional cell carcinoma (TCC) of the bladder, we studied 20 high-grade (Grade 3) TCCs from patients known to have limited disease (Jewett-Strong stages B1, B2, and C) and for whom at least 3-yr clinical follow-up was available. Data procured from this immunohistochemical analysis were compared with tumoral DNA content (determined by flow cytometry) and conventional clinicopathologic features. Overall, 13 of 20 TCC (65%) were reactive for p185-erbB-2. However, there was no apparent relationship between p185-reactivity and either DNA content, tumor stage or clinical outcome. These results suggest that c-erbB-2 expression may be augmented in localized high-grade TCC but that there is no evidence for the contention that this phenomenon has any effect on the biologic behavior of these neoplasms. The only factor that predicted a more favorable outcome was a relatively low stage at the time of diagnosis.