To learn if refractory periodontitis may be associated with defects in peripheral blood polymorphonuclear leukocyte (PMN) function, phagocytosis and chemotaxis were analyzed in 31 otherwise healthy patients and 12 unaffected controls. When compared to controls, no chemotactic defects to 10 nM f-Met-Leu-Phe (fMLP) were detected. In contrast, phagocytosis was significantly impaired (P < 0.001). The mean rates of adhesion and ingestion of opsonized Staphylococcus aureus by PMNs were 7.1 +/- 1.7 (+/- SD) and 1.4 +/- 0.5 bacteria/100 PMNs/minute respectively for patients, and 11.0 +/- 2.4 and 3.1 +/- 0.6 for unaffected, healthy controls. While the quality of oral hygiene and access to dental care were high, a retrospective search for associated environmental variables showed that 90% (28 of 31) of the refractory patients were smokers. The frequency of smokers is particularly striking, since only 21% of adults in Minnesota use tobacco regularly. These data suggest that there is a strong association between a peripheral blood PMN defect and refractory periodontitis. Furthermore, these studies suggest that tobacco use may contribute to this association.