Major life-threatening incidents involving hazardous substances are fortunately uncommon, but less devastating local events of this type are frequently encountered. Often the exposures involved are unknown and the health effects to be anticipated are uncertain. Physicians involved in the management of such incidents, or in the evaluation of patients who believe they may have sustained a significant exposure, must proceed methodically and with a knowledge of the most likely health outcomes. The first step is to evaluate the problem, documenting evidence and obtaining accurate information on the nature and magnitude of the hazard. The second step is to contain the problem, coordinating efforts with responsible public and private agencies. The third step is to evaluate health effects, focusing on specific outcomes when the exposure is known and on the primary organ systems of concern (dermal, respiratory, hepatic, neurologic, and renal) and carcinogenic and fetotoxic effects when the exposure is not known. Advance preparation can minimize the effect of an incident on an affected community.