A system and methods of the present invention advantageously provide efficient mail processing and handling that, as compared to existing procedures, enhances detection within the mail being processed or handled of biological, germ, chemical, or other harmful agents. A system and methods provide additionally a higher level of quality and consistency for processing and handling mail so that concerns over contamination of postal workers and potential mail recipients are reduced. A system and methods further provide enhanced disabling of contaminated mail contents, mail, mail equipment, mail containers, and mail personnel due to exposure or contact with harmful agents associated with mail. The system and methods preferably includes the use of at least one harmful agent sensor associated with mail processing equipment, and the at least one harmful agent sensor preferably includes at least one of the following: an olfactory device, an ultraviolet device, an infrared device, an x-ray device, a laser device, and a heat sensing device.