Mast cell-released histamine has been implicated in the enhanced acute inflammatory response of copper-deficient rats. The present study examined possible changes in the copper-deficient mast cell which may account for increased macromolecular leakage and edema formation. Mast cell populations were determined in the cremaster muscle of copper-adequate and copper-deficient rats. Total histamine content, unstimulated histamine release and concentration-dependent histamine release with the mast cell secretagogue compound 48/80 were also determined in isolated peritoneal mast cells. A significantly higher number of mast cells were found in the cremaster muscle of the copper-deficient rats (78 +/- 7 cells/5 microns section) than in the copper-adequate controls (51 +/- 4). Total histamine content per cell as well as unstimulated and stimulated release of the inflammatory mediator per cell were not different between the groups. The results suggest that dietary copper deficiency increases the mast cell population but does not alter the mast cell histamine content or sensitivity to degranulation in the rat. This increase in the number of mast cells may be a mechanism by which acute inflammation is enhanced in copper deficiency.