OBJECTIVES: Cardiovascular autonomic nervous system (ANS) activity estimated by analysis of heart rate variability (HRV) was compared in Helicobacter pylori-positive and H. pylori-negative male patients suffering from atypical chest pain to verify the hypothesis that autonomic neural system might be the way linking chronic H. pylori infection with gastrointestinal tract disorders. METHODS: We have analysed data obtained from 101 male patients examined in our clinic due to atypical chest pain, without evidence of serious cardiovascular, respiratory and digestive tract or metabolic diseases. In each patient, besides interview and physical examination, were performed: gastroscopy with mucosa biopsy (for urease test and histology), oesophageal pH-metry and manometry, ultrasound abdomen examination, chest X-ray, exercise test on running track, 24-h ECG Holter monitoring with time-domain and frequency-domain HRV analysis, and echocardiography. RESULTS: In comparison with H. pylori-negative, in all H. pylori-infected patients (n = 63) a significantly greater low frequency power, an index of sympathetic activity, and higher values of vagal tone parameters [pNN50, percentage of differences between RR intervals that are greater than 50 ms; high-frequency power in HRV analysis (HF)] were observed. The relationship between H. pylori infection and the HF value was confirmed in multi-factorial analysis. The aforementioned ANS activity differences were accompanied by: significantly fewer gastro-oesophageal acid reflux episodes, lower gastric acidity and more effective and complete oesophageal peristalsis in H. pylori-positive patients. CONCLUSIONS: H. pylori infection may affect ANS activity and via this way also contribute to gastro-oesophageal and cardiovascular pathology.