Attachment of bacillus Calmette-Guerin (BCG) organisms to the bladder during intravesical therapy is thought to be mediated exclusively by the glycoprotein fibronectin, which is expressed variably on epithelial surfaces and on basement membranes. We examined the relationship between the degree of fibronectin expressed on surgical specimens obtained from 50 candidates for BCG therapy and the subsequent clinical response. Immunoperoxidase staining for fibronectin was performed on tumor, nonadjacent normal mucosa and basement membrane tissues, and the intensity of the staining was scored on a scale of 0 to 3+ (control 2+). In the absence of recurrence at quarterly surveillance cystoscopy, a course of Tice BCG therapy consisted of 6 weekly and 12 monthly instillations. Recurrence of noninvasive tumor prompted a second BCG course. Followup ranged from 24 to 66 months (median 40 months). Of the 50 patients (11 with carcinoma in situ) disease progression occurred in 9 (none with carcinoma in situ). Compared to the results for tumors or for basement membranes, the degree of fibronectin expression on normal mucosa was well correlated with the clinical response (r = 0.59, p < 0.001 by Kendall Tau B). Routine assessment of fibronectin expression on the normal mucosa associated with superficial bladder cancer may be useful for predicting the clinical response to BCG therapy.