The induction of transitional cell bladder tumors following portacaval shunt (PCA) in rats was investigated. Thirty-five (29 males; 6 females) out of 86 animals developed a carcinoma. The highest incidence of tumors (73%) was seen in control animals without a PCA but with implantation of a bladder stone. PCA rats had an induction rate of 34% and a spontaneous bladder tumor was seen in 2/13 sham-operated controls. All rats with a bladder tumor also had urolithiasis; 34 rats had bladder stones in 1 rat had kidney stones. The induction rate in males was 29/52, 55.7% compared to 6/34, 17.6% in females. All tumors were transitional cell carcinomas and were graded G0-GIII [1(G0); 24 (GI); 1 (GI-II); 9 (GII)] accompanied in 20 cases by squamous cell metaplasia. Chronic irritation by stones and infection are the most likely causes of tumor development; however, other mechanisms such as excretion of carcinogens or tumor promoters cannot be completely excluded. The sex difference in stone formation - and tumor induction - are subject to further investigations.