Experimental induction of bladder cancer using N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is a well-established technique because of its convenience and reliability. However, most BBN-induced rat bladder tumors are superficial growths and are not usually considered a suitable model for deeply invasive human bladder cancers. We administered rats BBN for 20 weeks by mixing it in the drinking water at a concentration of 0.05%. The tumor which developed in the bladder was mechanically irritated by partial cystectomy, and the tumor was observed at intervals. Deeply invasive tumors developed with a high incidence after 6 weeks (75% 6 weeks after the partial cystectomy, 85% after 8 weeks and 71% after 12 weeks). In contrast, the incidence was 0% in the prepartial-cystectomy group, 8% in the control group and 22% 4 weeks after the partial cystectomy. The tendency for superficial tumors to become deeply invasive after 6 weeks was significant (p less than 0.005). No infiltration was seen in other organs including the prostate. The malignancy of the tumors was G1 and G2 at 0 week after the partial cystectomy, and G2 and G3 at 4, 6, 8, and 12 weeks. The rat bladder cancers induced by BBN in our experimental system seem to be a good model for deeply invasive human bladder cancers in terms of both the depth and malignancy of the cancers. In a clinical study on patients who underwent partial cystectomy, the recurrence rate was high, i.e., 50%, while mortality was as high as 40% or more in the high-stage and high-grade tumor group.(ABSTRACT TRUNCATED AT 250 WORDS)