The growth of the human gastrinoma model (PT) in athymic nude mice is stimulated by bombesin (BBS), an amphibian peptide homologous to both human gastrin-releasing peptide (GRP) and neuromedin B (NMB). The mechanism is not known, and a potent and specific GRP-R antagonist BIM26226, which has low affinity for NMB-R, was used in vivo in athymic nude mice bearing gastrinoma subcutaneously. Both the BBS and BIM26226 stimulated the growth of PT, and the growth stimulation was even greater when given together. RT-PCR study of gastrinoma revealed the presence of both GRP-R and NMB-R mRNA, but much more abundant NMB-R mRNA. We conclude that BBS-stimulated growth of gastrinoma involves both GRP-R and NMB-R, and our findings suggest that GRP-R mediates negative and NMB-R produces positive growth effects on gastrinoma.