Staphylococcus aureus is an important cause of skin infections. We recently described an outbreak of recurrent furunculosis involving methicillin-resistant S. aureus among mentally retarded adults. We sought to determine the role of impaired neutrophil functions in its pathogenesis. Blood neutrophil functions were determined during both the outbreak (1997) and a disease-free period (2000). Chemotaxis was measured by migration toward formyl-methionyl-leucyl-phenylalanine (FMLP), specifically and randomly; phagocytosis of opsonized zymosan (OZ) was assessed by microscopy; superoxide production was determined by cytochrome c reduction in unstimulated neutrophils and after stimulation with 50 ng/ml phorbol myristate acetate, 1 mg/ml OZ or 5 x 10(-7)M FMLP. Functions were compared between recurrent furunculosis (n=10) and non-recurrent furunculosis patients (n=13). During 2000, functions were normal among the 23 subjects, except for specific/nonspecific chemotaxis (mean 68%+/-26 and 69%+/-28). During infection, recurrent furunculosis patients had a significantly increased basal superoxide production as compared to disease-free period (10.5+/-4.7 vs. 4.9+/-1.9 nmol O(-)(2)/10(6) cells/min, p=0.003). During the disease-free period, recurrent furunculosis patients had lower basal superoxide production (4.9+/-1.9 vs. 7.7+/-3.5, p=0.067) and impaired specific chemotaxis (57%+/-28 vs. 76%+/-21, p<0.05) as compared to non-recurrent furunculosis patients. Only specific chemotaxis was an independent risk factor for recurrent furunculosis. Mentally retarded adults have impaired chemotaxis, with recurrent furunculosis cases having an even greater impairment. Abnormal specific chemotaxis is an independent risk factor for recurrent furunculosis. Impaired neutrophil functions thus have a role in the pathogenesis of outbreaks of recurrent furunculosis.