To assess the role of crystallinity in biological response, we quantitated the generation of reactive oxygen metabolites in human polymorphonuclear leukocytes (PMN) with a chemiluminescence assay using three hydroxyapatite preparations with sintering temperatures of 1,200°C and 900°C and a drying temperature of 110°C on the basis of equal weights (1 mg/ml). These crystals have almost the same average diameters and similar average zeta potentials. The crystals prepared at higher temperatures have higher crystallinity, or larger domain sizes, which were calculated by X-ray diffraction line broadening. The production of reactive oxygen metabolites by PMN in hydroxyapatite of 1,200°C was 10-times that by PMN in hydroxyapatite of 900°C and more than 50-times greater than that in hydroxyapatite of 110°C. A single linear correlation was observed for a plot of log (peak chemiluminescence levels) vs. a plot of log (domain sizes). These results clearly show that the maximal effect of crystallinity on hydroxyapatite-induced production of reactive oxygen metabolites by human PMN was seen at higher crystallinity.