It is well known that patients with insulin-dependent (or type I) diabetes mellitus are at high risk for bacterial infections. Since conflicting results have been reported on non-specific immune responses in type I diabetes, polymorphonuclear cell (PMN)-mediated phagocytosis and superoxide anion (O2-) generation in a group of individuals with well-controlled type I diabetes mellitus were assessed. Results showed that diabetic subjects were characterized by a significant impairment of phagocytic capacity when compared with healthy donors, while O2- release mimicked that seen in controls. Cell pretreatment with beta-hydroxybutyric acid (beta-HB) gave rise to a significant reduction in either phagocytosis or O2- production by PMN from type I diabetic individuals. Finally, beta-HB and glucose mixture supplementation to PMN suspensions did not induce any modification of their functional activities in comparison with those exerted by cells treated with beta-HB only. A disease-related or beta-HB-mediated PMN dysfunction in insulin-dependent diabetes mellitus is indicated.