Recently, the effectiveness of pentadecapeptide BPC 157 and other anti-ulcer agents, called 'direct cytoprotection', was evidenced in totally gastrectomized rats duodenum challenged with cysteamine 24 h after surgery, and sacrificed 24 h after ulcerogen application. The further focus was on the possibility that this effect could be seen over a more prolonged period (1, 2, 4 weeks), and in other parts of the gastrointestinal tract (i.e. oesophagus). After the removal of the stomach, the oesophagus and jejunum were joined by a termino-lateral anastomosis. The animals were euthanized 7, 14 or 28 d after surgery, when oesophagitis was blindly assessed both macroscopically (percentage of ulcerations areas) and microscopically (percentage of areas of ulcers, regeneration and hyperplasia; number of inflammatory cells - polymorphonuclear and mononuclear). Starting 24 h after surgery, the medication was continuously given in the drinking water, in a volume of 12.5 mL/rat daily, until euthanasia at the end of the observation period, i.e. 7, 14, 28 d following surgery. Based on previous experiments, the doses of agents were daily calculated per kg b.w. as follows: BPC 157 125 mg or 125 ng, cholestyramine 2.5 mg, ranitidine 125 mg, sucralfate 725 mg, whereas controls received 72.5 mL x kg(-1) water. In support of these initial findings, and considering gastrectomized acid-free rats as an ideal model for long-term cytoprotective studies as well, pentadecapeptide BPC 157 markedly attenuated termino-lateral oesophagojejunal anastomosis-reflux oesophagitis also over a quite prolonged period. This efficacy was only partly shared by other anti-ulcer agents. After 1-week-old oesophagitis (microscopical assessment), but not after 2 or 4 weeks, less damaged mucosa was noted in rats drinking ranitidine or sucralfate compared to controls. Similar effectiveness was noted for cholestyramine. The obtained results were supported also by inflammatory cell assessment. Compared with control values, BPC 157-treated groups consistently presented less polymorphonuclears and less mononuclears in all assessed periods. Interestingly, the values obtained in other treated groups showed no difference compared with control values. Thus, despite limitations, a generalization supporting a direct importance of a common cytoprotective approach, could be clearly provided. A useful, long-lasting cytoprotective activity (apparently more prominent in BPC 157 rats, than in reference agents, ranitidine, sucralfate, as well as cholestyramine) may be a likely suitable therapy in otherwise resistant reflux oesophagitis conditions.