In order to determine whether hydroxyapatite modulates the response of polymorphonuclear leukocyte (PMN) to oxidative stimuli, human PMNs were incubated with a non-activating concentration (1 or 10 micrograms/ml) of hydroxyapatite prior to stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP; 0.1 or 1 microM), phorbol 12-myristate 13-acetate (PMA; 100 pg/ml), sodium fluoride (50 microM), zymosan (1 microgram/ml), or the calcium ionophore A23187 (0.1 microM). Chemiluminescence was measured with an automatic microcomputer-controlled luminescence analyzer at 37 degrees C. Hydroxyapatite alone did not stimulate chemiluminescence at concentrations below 10 micrograms/ml. Levels 300-400% higher than 'stimulus only' controls without preincubation with hydroxyapatite have been recorded. This synergism between hydroxyapatite and subsequent stimuli reveals a new activity of hydroxyapatite and suggests that particulate material may prepare PMNs for an exaggerated inflammatory response to other phlogistic mediators. This is the first report demonstrating PMNs primed with particulate material.