In previous studies we have demonstrated a hydrogen ion concentration gradient across the mucus on rat and rabbit fundic mucosa, in vivo and in vitro respectively, observations which support the possibility of a 'mucus-bicarbonate' protective barrier. In the present studies we have demonstrated a similar gradient across the mucus on human gastric mucosa in vitro. The minimum mean hydrogen ion concentration at the mucus-epithelium interface was 1 . 1 X 10(-4) mM (pH 6 . 96, n = 10) when the luminal concentration was 5 . 6 mM (pH 2 . 25). Aspirin (10 mM) and N-acetyl cysteine (306 mM) (5%) increased the minimum intra-mucus hydrogen ion concentration and the gradient was overwhelmed by a luminal hydrogen ion concentration of 40 mM (pH 1 . 4). These results suggest that a hydrogen ion concentration gradient exists across the mucus on human gastric mucosa and that potential damaging agents may act by compromising one or other of th components of this 'mucus-alkaline', presumed 'mucus-bicarbonate', barrier.