Since Helicobacter pylori is isolated very frequently from gastric ulcer specimens, the combination therapy of antimicrobial agent and proton pump inhibitor has recently been used. A study was made on whether cefdinir (CFDN), amoxicillin (AMPC), metronidazole (MNZ), omeprazole (OPZ), and omeprazole-M (OPZ-M) have antimicrobial activity against H. pylori and whether they can inhibit H. pylori-producing urease. 1) CFDN, AMPC and MNZ showed a potent antimicrobial activity against H. pylori, and especially, AMPC showed a marked bactericidal activity in a short time. 2) OPZ is reported to be converted to OPZ-M, and active form, in the body. OPZ and OPZ-M showed a moderate antimicrobial activity against H. pylori, and scarcely any bactericidal activity. 3) CFDN and OPZ or AMPC and OPZ in combination did not show any synergistic effect on the antimicrobial activity, but MNZ and OPZ in combination showed additive effect on the antimicrobial activity against H. pylori. 4) OPZ and OPZ-M inhibited H. pylori-producing urease and the inhibitory effect of OPZ-M was more stronger than that of OPZ. CFDN, AMPC and MNZ did not show any inhibitory effect on H. pylori-producing urease at 10 micrograms/ml. From these data, antimicrobial agents and proton pump inhibitors in combination are expected to exert the in vivo synergistic effect since these drugs eradicate H. pylori and inhibit H. pylori-producing urease.