This experiment examined whether hepatic metallothionein (MT) synthesis induced by stressful stimuli could reinforce the peripheral leukocyte defense mechanism in mice. A 2 x 2 cm section of dorsal skin was excised from male ICR mice (7 w.o.), then the hepatic MT concentration and superoxide anion production (SOA) in peripheral leukocytes were measured at 6 and 24 hr after the excision. The 6 hr-hepatic MT level was 6 times greater in the skin-excised mice than in the controls. SOA in the skin-excised mice was 2.3 times greater at 6 hr than in the controls, then decreased to the control level by 24 hr. Food deprivation increased the hepatic MT and SOA levels at 24 and 48 hr to a remarkably greater level than in the controls. The increases in SOA, which was measured by chemiluminescence response (CL) were found to be due to an increase in the number of polymorphonuclear leukocytes (PMNs) in the peripheral leukocytes in both the skin excision and food deprivation groups. These results suggest that skin excision causes an inflammatory response in mice that results in an acute increase in the number of PMNs concomitant with the acute activation of hepatic MT synthesis. Food deprivation might result in physiologic stress 24 hr or more after food deprivation and cause "emergency" increases in MT synthesis and PMN defense mechanisms. Thus, some unknown linked mechanisms might exist between hepatic MT synthesis and increased peripheral PMNs.