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It has been demonstrated that Na+ down-regulates IgE-dependent and IgE-independent histamine release from basophils of normal subjects. The aim of this study was to evaluate whether Na+ exerts its inhibitory effect on basophil histamine release in patients with systemic sclerosis (SSc). Peripheral blood leucocytes were stimulated with anti-IgE, N-formyl-methionyl-leucyl-phenyl-alanine (fMLP) and IL-3 in the presence of high and low Na+ concentrations, and histamine release was measured by a fluorometrie method. The dose--response curves of histamine release induced by the above stimuli were similar in SSc patients (n = 15) and in normal subjects (n = 39). Na+ removal from the extracellular medium and its isosmotic replacement with choline chloride led to a significant increase of anti-IgE- and fMLP-induced histamine release in normal subjects, but not in SSc patients. In the former population, histamine release induced by an optimal dose of anti-IgE (&frac15000;) was 26.4 ± 3.1% in high Na+ and 59.3 ± 3.5% in low Na+ (mean ± s.e.m., P < 0.0001), whereas in the latter population mean histamine release was 20.4 ± 5.1% in high Na+ and 15.8 ± 2.9% in low Na+ (P NS). A similar trend was observed when basophils were stimulated with fMLP. Na+ exerted a dose-dependent inhibitory effect on anti-IgE- and fMLP-induced histamine release in normal subjects, but not in SSc patients. IL-3-induced histamine release from basophils of SSc patients was increased in a low-Na+ solution, but to a lesser extent when compared with normal controls. Therefore basophils from normal subjects and SSc patients behave in a different way when stimulated in a low-Na+ medium. The inhibitory effect of Na+ on basophil histamine release is impaired in SSc patients, and this abnormality could contribute to basophil dysfunction. [ABSTRACT FROM AUTHOR]