An enhanced activity of Na(+)/Li(+) countertransport, studied as a surrogate of Na(+)/H(+) exchanger, has been described in red blood cells of patients with cardiac syndrome X. In this study we investigated whether abnormalities in the activity of platelet Na(+)/H(+) exchanger (NHE) also existed in syndrome X patients and whether such abnormality was associated with platelet activation. Platelet NHE activity was evaluated in 21 syndrome X patients and 18 controls by measuring the pH recovery in platelets after acid loading and/or thrombin stimulation. The linear correlation existing between the initial intracytoplasmic pH (pH(i)) values and the maximal velocity of pH recovery allowed to calculate the values of slope and intercept at pH(i)=6.6 (I(pH6.6)) for each individual. Urinary excretion of the major TXB(2) metabolite, 11-dehydro-TXB(2) was measured in 15 syndrome X patients and 15 controls. The acidification-induced NHE activity resulted significantly higher in syndrome X patients compared to controls. Indeed, slope values were 0.75+/-0.29 and 0.5+/-0.23 min(-1) in patients and controls, respectively (P=0.01), while I(pH6.6) values were 0.24+/-0.1 and 0.17+/-0.1 DeltapH/min (P=0.04). The thrombin-stimulated NHE activity, however, was not different in the two groups and no significant difference in the urinary excretion of 11-dehydro-TXB(2) between patients and controls (median 920 vs. 765 pg/mg creatinine, respectively) (P=0.32) was also found. Thus our data demonstrate an alkaline shift in pH-dependence of platelet NHE of syndrome X patients. This abnormality does not seem to be associated with increased platelet activation.