The Pfiesteria organism was first identified and named in the early 1990s and its ability to kill fish was documented at the time. Research on the effects of exposure to its toxin on humans is more recent, sparked largely by widely publicized fish kills in the late 1990s and reports of adversely affected persons present at the scenes of the kills. Consequently, the peer-reviewed literature is still limited and substantial research is in progress at institutions in the Atlantic coast states of Maryland, North Carolina, and Virginia, and elsewhere. Dramatic reports of fish kills and illness among persons exposed to water at the time of the kills sparked public concern and reviews by a variety of agencies in the late 1990s. The primary data sources, secondary reviews, and expert panel reports were evaluated by this panel.In approaching its charge, the panel turned to a toxicologically based framework for conducting its review, characterizing the state of the science, and identifying research gaps (Figure 1). Prevention of adverse effects of Pfiesteria will need to be based in an understanding of each element in this framework: the ecological factors that drive concentrations of the organism and its state; the stimuli that lead to toxin production and the nature of the toxin; the mechanism of the toxin's effect on fish; the circumstances and routes of human exposure; and the mechanisms by which human health is adversely affected by the toxin. Sufficient certainty is needed on each of these points to evolve policies that will assure protection of public health and the fish populations. In addition, we need enhanced understanding of the still poorly characterized effects of Pfiesteria on human health.Other reviewers have commented on many elements of this framework; their reviews make clear that there are gaps in scientific understanding, with attendant uncertainty for decision makers, for each of these elements. With substantial research now under way, the panel views the timing of this review as an opportunity to examine the gaps and the extent to which new research findings will set aside uncertainties.Pfiesteria has proved to be a challenging problem. Researchers have referred to the organism as "ephemeral" and "phantom-like."It has multiple forms, transforming itself into a toxin-producing dinoflagellate when it somehow senses the presence of fish. Its toxin apparently destroys the integrity of the skin of fish, allowing the organism to feed; after feeding, the organism transforms into a dormant form. (Throughout this report, we refer to "Pfiesteria toxin," recognizing that the organism may well produce more than one toxin. We use the plural "toxins" in describing the basis for supposing that more than one toxin exists.) There is debate as to whether a pathognomonic lesion occurs in fish. Humans seem to be at risk when their activities lead to contact with toxin-containing water at the time of fish kills. Whether the toxin reaches target tissues by dermal contact or inhalation is unclear. A diffuse syndrome has b...