Diagnostic tests on saliva have advantages compared with those on serum. In 119 consecutive dyspeptic patients referred for endoscopy we developed and validated an enzyme-linked immunosorbent assay to detect salivary immunoglobulins to Helicobacter pylori. Salivary IgG distinguished positive and negative cases (p < 0.0001), but salivary IgA did not. The optimum performance of salivary IgG (85%) was similar to that of serum IgG (90%) and better than that of salivary IgA. Using our assay and a history of regular use of non-steroidal anti-inflammatories in screening patients under 45 years, we detected all peptic ulcers while saving 39% of endoscopies.