Reduction in acid secretion in atrophic gastritis allows bacterial colonization of the stomach, most extremely in achlorhydric patients with pernicious anaemia, in whom overgrowth may cause nitrate reduction and formation of potentially carcinogenic N-nitroso compounds. Subsequent bacterial contamination of the upper small intestine can induce mucosal damage and malabsorption. The situation is similar after gastrectomy. In achlorhydria and after gastrectomy, the risk of gastric cancer is increased. There is controversy as to the risks of long-term treatment with H2-receptor antagonists. Increase in nitrate-reducing bacteria, nitrite and N-nitrosamine have been observed in patients by some investigators but not in volunteers and patients by others. Bacterial concentrations after cimetidine are inversely related to pretreatment acid secretory capacity. Demonstration of increased mutagenicity of gastric juice after H2-receptor antagonists gives grounds for caution. Drastic acid reduction may in future be reserved for short-term and intermittent treatment and mild or moderate reduction for long-term treatment of peptic ulcer and ulcer prevention.