A total of 144 gastric biopsies colonized by Helicobacter-like organisms were studied under light and differential interference contrast microscopy for the modes of bacterial colonization. Biopsies were also graded for the degree of epithelial damage (epithelial-damage-grade: 0 to 6, in ascending order of severity) and density of Helicobacter-like organism (Helicobacter-grade: 0 to 6, in ascending order of bacterial density). Three modes of colonization were identified: free-in-mucus, surface-adhesion and intercellular colonization. Because light microscopy cannot definitely prove the presence of intracellular colonization, bacteria located between cells and below the apical cell border were counted together as intercellular colonization. Bacteria free-in-mucus were seen in all biopsies. Surface adhesion was seen in 50-87.9% of biopsies, without obvious correlation with the epithelial-damage- and Helicobacter-grades. The incidences of intercellular and intracellular colonization were directly proportional to the epithelial-damage- and Helicobacter-grades. Free-in-mucus as the predominant mode of colonization was mainly seen in biopsies with lower (1-3) epithelial-damage- and Helicobacter-grades. Conversely, biopsies with intercellular colonization as the predominant mode of colonization were mainly cases with higher (4-6) epithelial-damage- and Helicobacter-grades. In cases showing predominantly bacteria between cells, 69.2% had a gastric ulcer whereas only 38.8% of cases showing predominantly bacteria free-in-mucus showed ulceration (P < 0.01). These results indicate that Helicobacter-like organisms can invade and penetrate between epithelial cells. When free-in-mucus, Helicobacter-like organisms are less likely to induce epithelial damage. However, the more invasive modes of colonization (intercellular) were associated with severe epithelial damage and high Helicobacter density.(ABSTRACT TRUNCATED AT 250 WORDS)