Fifty-four clinical isolates of Helicobacter pylori from human gastric biopsy specimens were tested for cytotoxin production, as determined by intracellular vacuolization of HeLa cells, and for the induction of oxidative burst in human polymorphonuclear leukocytes (PMNLs), as measured by luminol-enhanced chemiluminescence (CL). Nonopsonized, 20 of the H. pylori strains induced a rapid and strong CL response, in contrast to 30 other strains, which showed only weak and slow responses. Another four strains gave inconclusive results. Cytotoxin production was demonstrated in 10 of the 20 strains with rapid responses but only in 3 of the 30 strains with slow and low responses (p = 0.0027, Fisher's exact test, two-tailed). Eleven of the 15 cytotoxin-producing strains (p = 0.0135) and 13 of the 20 strains with strong CL responses (p = 0.0209) were from 22 patients with peptic ulcer disease (PUD). The ability of some nonopsonized H. pylori to activate PMNLs showed co-variation with their ability to produce cytotoxin, but these two properties seem to be independent markers of PUD.