The antiulcer effect of verapamil, and its relationship to stomach calcium levels, were examined in rats restrained at 4 degrees C (stress). Stress for 2 hr significantly increased muscle calcium and induced mucosal ulceration in the gastric glandular segment; calcium concentrations in the glandular mucosa and serum were unaffected. Verapamil or calcium gluconate given 30 min before stress prevented the rise in gastric muscle calcium, and attenuated ulcer severity. Bis(beta-aminoethylether)-NNN'N'-tetra-acetic acid (EGTA) pretreatment, however, further elevated stomach muscle calcium and markedly worsened lesion formation. These findings suggest that increased stomach muscle calcium could be a causal factor in stress-induced gastric glandular ulceration.