To survive adverse conditions, some bacterial species are capable of developing into a cell type, the "spore," which exhibits minimal metabolic activity and remains viable in the presence of multiple environmental challenges. For some pathogenic bacteria, this developmental state serves as a means of survival during transmission from one host to another. The spores are the highly infectious form of these bacteria. Upon entrance into a host, specific signals facilitate germination into metabolically active replicating organisms, resulting in disease pathogenesis. In this chapter, we will review spore structure and function in well-studied pathogens of two genera, Bacillus and Clostridium, focusing on Bacillus anthracis and Clostridium difficile, and explore current data regarding the lifestyles of these bacteria outside the host and transmission from one host to another. Bacillus anthracis and Other Pathogenic Bacillus Species The Bacillus species are Gram-positive, spore-forming, facultative aerobes that are commonly found in the soil, sometimes associated with plants and nematodes. The Bacillus cereus sensu lato clade of this well-studied genus contains pathogens and nonpathogens, with a complex taxonomy that in recent years has been continuously modified to reflect DNA sequence data. In addition to DNA sequence similarities and gene synteny, horizontal transfer of closely related plasmids is apparent among these ubiquitous soil bacteria (1). Member species of the Bacillus cereus sensu lato group include B. cereus sensu stricto, B. anthracis, Bacillus thuringiensis, Bacillus mycoides, Bacillus pseudomycoides, Bacillus weihenstephanensis, and Bacillus cytotoxicus (2-10). Of these, the most well-studied species are B. anthracis, B. cereus sensu stricto, and B. thuringiensis. B. anthracis is the causative agent of anthrax in mammals, an often-lethal disease. Human disease is generally acquired accidentally during outbreaks of anthrax in domestic livestock and wildlife, but has also been associated with bioterrorism (11). Certain strains of B. cereus can cause food poisoning in humans, while some strains of B. thuringiensis are lethal for invertebrates and are used as insecticides (12, 13). Other species of the B. cereus sensu lato group are only occasionally cited as disease causing in mammals but their potential virulence factors are not known. B. anthracis and anthrax-B. anthracis infection can manifest as a cutaneous or systemic disease. Entry of spores via a preexisting lesion in the skin can result in cutaneous anthrax. This disease is distinguished by the presence of a characteristic, black eschar on the skin, and typically remains a localized infection. Systemic anthrax can take several forms.