Altered intracellular Ca2+ concentration is a pivotal regulatory mechanism of leukocyte function. Since polymorphonuclear neutrophils (PMN) are involved in traumatic organ dysfunction, we prospectively investigated Ca2+ regulation and function of circulating PMN multiple trauma patients (Group A: ISS < 27; Group B: ISS > or = 27). Circulating PMN were isolated during 12 days, followed by determination of formyl-methionyl-leucyl-phenylalanine (fMLP)-induced PMN-superoxide production (PMN-SOP) by SOD-inhibitable ferricytochrome C reduction, and PMN cytosolic Ca2+ concentration ([Ca2+]i) by fluorescent fura2/AM (340/380 ratio). PMN-SOP was significantly higher in Group B (mean ISS: 39.9 +/- 2; n = 21) at day of admission than in controls and Group A (mean ISS: 18.2 +/- 1; n = 22) (P< 0.05). In Group B, the significant rise of basal [Ca2+]i between Day 2 and Day 4 was associated with significant lower PMN-SOP during that period (P < 0.05). The fMLP-induced [Ca2+]i response was supranormal in both groups. PMN-elastase concentrations were substantially higher in Group B compared with Group A until Day 4. Circulating IL-6, IL-8, and soluble TNF-receptor (55 kD) were significantly increased in Group B compared with Group A at the day of trauma (P < 0.05). Severe trauma is characterized by a biphasic pattern of neutrophil priming characterized by early increase and secondary suppression. The association of depressed neutrophil superoxide production (deactivation) and elevated basal [Ca2+]i suggests Ca2+-mediated disturbance of neutrophil NADPH-oxidase metabolism.