The relation between use of histamine-2-receptor (H2-receptor) antagonists and gastric cancer risk was investigated in a case-control study in northern Italy. 563 patients with newly diagnosed, histologically confirmed gastric cancer were compared with 1501 controls who did not have neoplastic or gastrointestinal disorders. 36 (6.3%) cases and 59 (3.3%) controls had used H2-receptor antagonists (cimetidine or ranitidine). The relative risk (RR) for ever-use was 1.8 (95% confidence intervals [CI] 1.2, 2.7). The increased risk was restricted to patients who had started treatment with H2-receptor antagonists within 5 years of the diagnosis of stomach cancer (RR 3.1; 95% CI 1.8, 5.3). For first use of H2-receptor antagonists 5-9 years previously the RR was 1.5 (95% CI 0.7, 3.3), and for first use 10 or more years previously RR was 0.2 (95% CI 0.03, 0.8). Although the incidence of gastric cancer was raised for the first few years after the start of treatment with H2-receptor antagonists, this may reflect misdiagnosis of some early gastric cancers. The findings are against long-term persistence of an excess risk of gastric cancer in association with use of H2-receptor antagonists.