Several human studies have found that the bacterial product lipopolysaccharide (LPS), also known as endotoxin, may exacerbate existing asthma. However, other studies have shown that exposure to LPS in childhood can protect against developing asthma later in life. The latter finding is part of a larger body of epidemiologic evidence, known as the hygiene hypothesis, which links exposure to pathogens or their products in childhood to protection against developing asthma or atopy in adult life. Although the molecular and cellular mechanism underlying this relationship is not known, recent studies—carried out by the Immunogenetics Group—indicate that toll-like receptor (tlr)4 signaling attenuates pulmonary allergic responses to chronic challenge with aerosolized ovalbumin. The group is currently determining the cellular and molecular mechanisms that occur after exposure to low doses of endotoxin and that lead to the negative regulation of allergic inflammation in the lung.