Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer. While the optimal protocol for bacillus Calmette-Guerin remains to be determined, experience with 92 randomized and 30 nonrandomized (high risk) patients followed for up to 5 years provides information that may improve future protocols. Side effects of bacillus Calmette-Guerin are observed to increase with increasing frequency and duration of treatment. The protection from tumor recurrence has persisted: only 6 of 30 patients (20 per cent) treated with bacillus Calmette-Guerin have had recurrent tumor compared to 14 of 27 controls (52 per cent, p equals 0.008, chi-square test), and mean time to recurrence increased from 24 to 48 months (p less than 0.005, Savage). Skin test reactivity to purified protein derivative is particularly useful in predicting response to bacillus Calmette-Guerin immunotherapy. Currently, 60 patients have been randomized to receive bacillus Calmette-Guerin immunotherapy and only 1 of 22 patients (4.5 per cent) in whom the purified protein derivative skin test results converted from negative to positive has had recurrent tumor, compared to 12 recurrences (32 per cent) in patients whose skin tests were positive before treatment or failed to convert following treatment (p equals 0.014, chi-square). Seven recurrences (33 per cent) developed in 21 patients whose skin tests remained negative (p equals 0.015) and 5 recurrences (29 per cent) developed in 17 patients whose tests previously were positive (p equals 0.068, Fisher's test, not significant). The benefit of percutaneous bacillus Calmette-Guerin is suggested by the observations that the recurrence rate in patients treated with intravesical bacillus Calmette-Guerin alone is 40 per cent, and all 7 patients whose purified protein derivative skin tests were negative continued to have negative results when percutaneous bacillus Calmette-Guerin was omitted (p equals 0.003). Among high risk patients a marked decrease in or complete prevention of recurrent tumor was observed in 82 per cent of 22 patients treated previously with chemotherapy and 11 of 14 (78 per cent) with carcinoma in situ have had a complete response.