Release of potent lysosomal enzymes by degranulation of polymorphonuclear leukocytes (PMNs) in host gingiva may contribute significantly to tissue destruction and the pathogenesis of periodontal disease. A pilot study established that peripheral blood PMNs from humans with rapidly progressive periodontitis (RPP) contained significantly increased amounts of intracellular lysosomalβ‐glucuronidase as compared to healthy controls. This investigation gained insight into the question: are the increased levels ofβ‐glucuronidase in persons with RPP an apriorigenetically determined PMN characteristic, or a reactive phenomenon induced by the periodontal disease process during granulopoiesis? Twelve healthy controls and twelve otherwise healthy individuals with RPP participated in a repeated measures design of T0(initial, baseline), T1(four weeks after disease control therapy), and T2(two months later). At each visit clinical indices (GI, pocket depths, GCF flow, plaque index) were performed and peripheral blood obtained. PMNs were isolated and suspended as 5×106cells in 2.0 ml of HBSS. PMN suspensions were tested for total intracellularβ‐glucuronidase, degranulation induced by 1×10−6M and 5×10−7M FMLP challenges, and unchallenged for non‐specific enzyme release. PMNs from individuals with RPP contained significantly higher absolute amounts of β‐glucuronidase and released greater absolute amounts at FMLP challenge at T0, T1, and T2compared to controls. No relationship was found between any of the clinical indices andβ‐glucuronidase levels and no pattern was discovered relating to the repeated measures over time. We conclude that RPP peripheral blood PMNs contain elevated levels ofβ‐glucuronidase that are not induced by the p