Tetracycline inhibition of neutrophil‐associated collagenolysis has been the focus of a number of investigations. Evidence has suggested that this inhibition results from the ability of this family of antimicrobial drugs to bind divalent cations such as Ca2+and Zn2+, two cations that are required for full expression of activity of metalloproteinases such as collagenase and gelatinase. Data presented in this study demonstrate that tetracyclines can also inhibit neutrophil‐mediated RBC lysis, superoxide anion synthesis, degranulation and migration. To some extent, tetracycline inhibition of neutrophil functions is mimicked by the Ca2+binding agents, EDTA and TMB‐8. However, Ca2+enrichment restored full function to EDTA‐ and TMB‐8‐treated cells but not to tetracycline‐treated neutrophils. This suggests that Ca2+binding plays a role but is not the critical effect leading to tetracycline suppression of neutrophil functions. It has been suggested that tetracyclines can suppress leukocyte‐associated tissue damage. Host tissues are protected from neutrophil‐mediated damage by two mechanisms: 1. Neutrophil granule‐associated enzymes are secreted in an inactive state; and, 2. tissues are protected from these enzymes by a potent inhibitor shield. Neutrophils can bypass these protective elements by activating enzymes and by destroying the shield through the synthesis of oxygen radicals. Therefore, tetracyclines may suppress neutrophil‐mediated tissue damage by inhibiting their migration and degranulation and, potentially more importantly, by suppressing synthesis of oxygen radicals. Before the anti‐inflammatory properties of the tetracyclines can be most safely and effectively used in treating conditions where inflammatory tissue damage is a significant part of the disease process, a more complete understanding of the mechanisms involved in their inhibition of PMN fu