Endoscopic subureteral injection has become an established alternative means for treating vesicoureteral reflux in select children. However, which injection material to use remains a controversy. Polytetrafluoroethylene (Teflon) has been injected in more than a thousand patients with few complications, although experimental and clinical studies have demonstrated migration of the injected particles into distant organs, such as the lungs and the brain, as well as local and metastatic granuloma formation. Therefore, we introduced, following experimental studies in the mini-pig model, glutaraldehyde cross-linked, highly purified bovine collagen for injection. Between June 1988 and October 1991, 97 refluxing ureters in 66 children were treated by endoscopic subureteral collagen injection. In 58.8% of the ureters reflux was cured after 1 and in 77.3% after 2 injections. Considering improvement to grades I and II reflux without further treatment as success, the success rate increased to 68.0% after 1 and to 89.7% after 2 injections. Mean followup was 18.5 months (range 3 to 39 months). After 2 failed injections the patients either returned to antibiotic long-term prophylaxis or the reflux was operatively corrected. The operative procedure was never compromised by the preceding injection. A direct correlation between deficient length of the submucosal tunnel of the intravesical ureter and the iatrogenic malposition of the collagen deposits, and the failures could be demonstrated. Granuloma formation at the site of injection was not found. The results of the histological investigation of the collagen deposits removed at open ureteral reimplantation for failures are reported. It could be demonstrated that endogenous fibroblasts invade the bovine collagen implant and that these cells show active production of new human collagen, types I and III, replacing the implant.