Only a minority of subjects with Helicobacter pylori infection develop clinical gastroduodenal disease. It is unclear whether host factors or bacterial virulence properties contribute to the pathogenic mechanisms. We have previously demonstrated a 25-35-kDa protein with phagocyte stimulatory activity in bacterial sonicates. Protein preparations were made from 15 H. neutrophil and monocyte chemotaxis and chemiluminescence was assessed with cells from healthy donors in comparison with N-f-methionyl-leucyl-phenylalanine and C5a anaphylatoxin. The potency of bacterial protein(s) for induction of monocyte chemiluminescence was significantly higher for strains from ulcer patients (1 +/- 1 microgram/ml induced > or = twofold increase of control response) and chronic active gastritis (1 +/- 1 microgram/ml) compared with superficial gastritis (> 1,000 microgram/ml, p<0.05). Neutrophil activation was also significantly more potent with strains from duodenal ulcer disease. The chemotactic activity of bacterial preparations was not significantly different between the groups. We conclude that bacterial strains with pronounced activation of phagocytes are associated with the presence of clinical ulcer disease, supporting the existence of ulcerogenic strains.