To investigate the mechanism of action of a series of potential combination therapies for use against Helicobacter pylori.The effects of certain anti-ulcer agents on the antimicrobial activity of antibiotics effective against H. pylori were determined in vitro.H. pylori was cultured on Skirrow's agar. Amoxycillin, clarithromycin, erythromycin and tetracycline were used. The anti-ulcer agents studied comprised aluminum chloride, sofalcone [2'-carboxymethyl 4,4'-bis(3-methyl-2-butenyloxy)chalcone] and zinc chloride. Urease activity was measured by the urease-indophenol method. The minimum inhibitory concentration was determined by a plating method, with H. pylori streaked on plates containing various concentrations of the antibiotics plus sublethal doses of the anti-ulcer agents.This in vitro study showed that sofalcone had a direct antibacterial effect and, in addition, inhibited the adhesive property of H. pylori. It did not inhibit the antimicrobial activity of the antibiotics amoxycillin, clarithromycin, erythromycin or tetracycline against H. pylori. The metal ions had inhibitory effects on the antimicrobial activity of amoxycillin, erythromycin and tetracycline, but not on that of clarithromycin.This study suggests that sofalcone is a suitable candidate for combination therapy.