For several years, our laboratory has been interested in evaluating if DNA repair capacity in peripheral human mononuclear leukocytes (HML) might be utilized as a marker of susceptibility to cancer. We have tested our hypothesis by using two different estimates of DNA repair, namely, unscheduled DNA synthesis (UDS) and ADP-ribosyl transferase (ADPRT) activity. Both UDS and ADPRT are sensitive to regulation by oxidative stress, and these parameters are suppressed in patients with cancer of the breast, colon, or lung, or with the genetic predisposition to develop it. Here we have considered interindividual variation in prooxidant-induced DNA repair in HML by analyzing ADPRT responses in regard to (1) constitutive ADPRT levels, (2) the levels of DNA damage induced by different prooxidant generating systems, (3) the type of oxygen radical generated, and (4) the role of antioxidant defenses. Only the constitutive level of ADPRT responses could explain the variation observed on 50 subjects. These data support a regulatory role for endogenous host factor variation in ADPRT and the likelihood of involvement of genetic factors.