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Background: Developmental and perinatal lead exposure in rats affects the Hypothalamus-Pituitary-Adrenal Cortex (HPA) axis function resulting in elevated corticosterone blood levels thus affecting the level of stress responsivity of the offspring. The majority of the studies on lead exposure and stress have been done by exposing the animal indirectly during gestation, or lactation periods. This study presents evidence supporting that short term lead exposure affects a stress-like response in adult lead-exposed mice., Material/methods: DBA/2J mice were exposed to three different lead concentrations, 250, 500 and 1000 ppm, in the drinking water for a two week period. After the exposure period the animals were subjected to behavioral tests, i.e., social contact, and the plus maze using a computer-assisted videomonitoring system, Videomex-V (Columbia Instruments). The levels of ACTH and corticosterone in plasma were also measured using a Radioimmunoassay (RIA)., Results: Exposed animals displayed a significant decrease in the length of time the mice pairs spent within social contact distance (5.18 +/- 0.58 seconds for controls and 3.23 +/- 0.34 seconds for 1000 ppm exposure), and a significant decrease in the percent of time the mice stayed in the open arms of the plus maze (7% for controls and 1% for 1000 ppm exposure) a measure indicator of anxiety. In addition exposed mice showed increased blood levels of ACTH (573 +/- 106 microg/dL for 1000 ppm and 127 +/- 25 microg/dL for control mice) and corticosterone (195.12 +/- 52.47 controls and 87.33 +/- 10.94 for exposed)., Conclusions: These results support the hypothesis that exposure to lead of the adult mice affects a behavioral and hormonal response consistent with stress.