Previous studies suggested that an enhanced pain sensitivity is present in patients with cardiac syndrome X(SX). We investigated whether SX patients present abnormalities in the electrical cerebral signals generated by pain stimuli. Methods and results: Cortical laser evoked potentials(LEPs) were recorded in 16 SX patients, in 10 patients with refractory angina due to obstructive coronary artery disease(CAD) and in 13 healthy controls. LEPs were recorded during stimulation of chest and right hand dorsum. Three sequences of painful stimuli were applied at each site. Subjective pain rating was assessed by a 0- 100 mm visual analogic scale(VAS). Basal LEPs did not differ among groups and there were no differences for most LEP components across the repetitions of stimuli. However, the amplitude of the N2/P2 LEP component, specifically reflecting cortical pain processing, decreased across the three sequences of stimuli in controls and CAD patients, but not in SX patients. Compared with the first sequence, the N2/P2 amplitude during the third sequence of stimuli in the three groups was 77± 16, 56± 24, and 99± 34% , respectively, for chest(P=0.001), and 63± 31, 72± 17, and 98± 46% , respectively, for right hand(P=0.03) stimulation. The changes in VAS pain score across the three sequences paralleled those of N2/P2 amplitude. Conclusion: Our data show that in SX patients, central handling of painful stimuli is characterized by inadequate habituation, which might play a role in determining the peculiar clinical characteristics of anginal chest pain of these patients. Previous studies suggest that an enhanced pain sensitivity is present in patients with cardiac syndrome X (SX). We investigated whether the SX patients present abnormalities in the electrical cerebral signals generated by pain stimuli. Methods and results: Cortical laser evoked potentials (LEPs) were recorded in 16 SX patients, in 10 patients with refractory angina due to obstructive coronary artery disease (CAD) and in 13 healthy controls. LEPs were recorded during stimulation of chest and right hand dorsum. Three sequences of painful stimuli were applied at each site. pain rating was assessed by a 0- 100 mm visual analogic scale (VAS). Basal LEPs did not differ among groups and there were no differences for most LEP components across the repetitions of stimuli. However, the amplitude of the N2 / P2 LEP component , specifically reflecting cortical pain processing, decreased across the three sequences of stimuli in controls and CAD patients, but not in SX patients. Compared with the The N2 / P2 amplitude during the third sequence of stimuli in the three groups was 77 ± 16, 56 ± 24, and 99 ± 34%, respectively, for chest (P = 0.001), and 63 ± 31, 72 ± The changes in VAS pain score across the three sequences paralleled those of N2 / P2 amplitude. Conclusion: Our data show that in SX patients, central handling of painful stimuli is characterized by inadequate habituation, which might play a role in determining the peculiar clinical characteristics of anginal chest pain of these patients.