The c-erbB-2/neu-encoded protein p185 is closely related to the growth and metastasis of adenocarcinoma. We sought to reverse the malignant phenotype of gastric cancer cell line SGC7901 with c-erbB-2-specific ribozyme. We designed the ribozyme and generated the in vitro transcription vectors of the ribozyme and its substrate. In vitro cleavage reaction indicated that the ribozyme catalyzed 79.3% target RNA in 1 hour at 37 degrees C. Then, we generated the eucaryotic expression vectors of the ribozyme and transfected them into SGC7901 cells, which highly express p185. Analyses showed that the c-erbB-2 mRNA and p185 were reduced remarkably in the ribozyme-transfected cells. The growth rate of the ribozyme-transfected cells was much lower than that of the control group. Tumorigenicity was also decreased dramatically in nude mice. The results demonstrated that c-erbB-2-specific ribozyme may inhibit the malignancy of gastric cancer cells SGC7901.