Nitric oxide (NO) is an endogenous bioregulator, a "second messenger" that mediates many critical biological processes, including parts of the immune response, some types of neurotransmission, cardiovascular homeostasis, and male sexual function. Of direct interest to FDA are drugs, devices and biologicals designed to deliver NO or regulate nitric oxide levels. These include the widely used nitro-vasodilator drugs such as nitroglycerine, medical devices delivering NO directly to patients, and biologicals interfering with toxic shock. Under development are products designed to deliver NO selectively without systemic distribution. Part of the biological response to implanted materials may be the induction of NO, recently detected around implants in rats (Jill James, NCTR). The many actions of NO are not yet understood; among its effects, we found that NO deaminates DNA and is mutagenic (Wink et al., Science 254: 1001, 1991). These results raise questions concerning the potential of NO-generating products to present a carcinogenic risk, and provide a testable hypothesis concerning the mechanism of solid-state carcino-genesis. Our current experiments seek to determine the relative susceptibility of bacterial systems with different DNA repair backgrounds to NO-mediated genetic damage, as an aid to risk/benefit analysis of NO-mediated therapies in humans.