Using differential screening we have cloned a cDNA encoding a novel oxidative stress protein designated A170 from murine peritoneal macrophages. It has a Zn-finger domain, a PEST domain and several potential phosphorylation sites for kinases. Treatments with oxidative stress agents such as diethyl maleate and paraquat increased a 2.0-kilobase A170 mRNA about twofold in the macrophages after 12 hours in culture. However, H2O2 or glucose/glucose oxidase did not increase the level of the A170 mRNA. Using an A170-specific antibody we have detected in the macrophages a 60-kDa protein that was induced 5 to 10 hours after the addition of the oxidative stress agents. A search of sequence databases revealed that the A170 protein is roughly 90% identical to a human protein that binds to the Src homology 2 domain of the T-cell-specific tyrosine kinase p56lck. These features suggest that the A170 protein plays a significant role in oxidative stress-responsive signal transduction in macrophages.