Metam sodium is the third most commonly used agricultural pesticide (by weight) in the U.S. A spill of 19,000 gallons of metam sodium into the Sacramento River in 1991 clearly demonstrated that a major uncontrolled release can have adverse ecological and human health effects. Furthermore, this incident revealed that estimates of Reference Exposure Levels for the major breakdown product of metam sodium (methylisothiocyanate, MITC) were reasonable with regard to the induction of discomfort. In fact, the irritant properties of MITC seem to account for many of the most commonly reported symptoms in this incident. However, neurotoxicity may also account for some of these symptoms. There is evidence that metam sodium can act as a contact sensitizer in humans, inducing allergic dermatitis. It also may exacerbate or induce respiratory allergy (asthma). The ecological impact of routine use of metam sodium is not clear, but adverse effects on non-target plants have been inferred from modeling studies, and adverse effects on soil microbes have been observed. These issues deserve further study. Human health effects of occupational or routine environmental exposure to metam sodium are not known, but there is limited evidence for immunological (hypersensitivity) and developmental effects as well as irritation and associated symptoms. Animal studies suggest a potential for immunological, developmental, carcinogenic, and atherogenic effects. Metam sodium and some of its breakdown products have a wide variety of molecular and cellular actions that could explain the health effects noted here. However, further studies are needed to relate specific molecular or cellular actions to specific health effects.