H+ secretion was studied in guinea pig fundic mucosa incubated in (A) bicarbonate-Ringer's gassed with 95% O2-5% CO2, or (B) HEPES gassed with 100% O2 before and after luminal pH was lowered to 2.0 for periods up to 90 min. At pH 2.0 for 60 min, H+ secretion in group A tissues fell by 35 +/- 4% (P = 0.02) from a control rate of 1.35 +/- 0.09 mu eq/cm2/hr and in group B tissues by 50 +/- 11% (P = 0.01) from a control rate of 1.59 +/- 0.08 mu eq/cm2/hr. After 90 min at pH 2.0, H+ secretion in group A fell by 53 +/- 8% (P = 0.02) from a control rate of 1.47 +/- 0.07 mu eq/cm2/hr and in group B fell by 44 +/- 6% (P = 0.01) from a control rate of 1.38 +/- 0.07 mu eq/cm2/hr. Histamine 1 x 10(-4) M stimulation following exposure to pH 2.0 for 90 min increased secretion in group A tissues from 0.80 +/- 0.14 to 1.06 +/- 0.13 mu eq/cm2/hr (P < 0.05), compared with an increase in nonacidified controls from 1.15 +/- 0.22 to 1.80 +/- 0.20 mu eq/cm2/hr (P < 0.05) and in group B tissues from 1.27 +/- 0.10 to 1.56 +/- 0.19 mu eq/cm2/hr (P < 0.05) compared with nonacidified controls from 1.43 +/- 0.22 to 2.23 +/- 0.41 mu eq/cm2/hr (P < 0.05). Secretory function and electrical characteristics were adversely affected by luminal acidification to pH 2.0 and suggested a breach in the mucosal barrier with damage to parietal cells.