Abstract: Karenia brevis (K. brevis), the microalgae responsible for Red Tide harmful algal blooms, regularly releases a suite of potent neurotoxic brevetoxins in southwest Florida and is intermittently responsible for massive marine life morbidity and mortality. While these blooms have been documented in the Gulf of Mexico since the 16th century, evidence suggests that their frequency and intensity have been increasing in recent decades, most likely driven by human development in Florida and higher Gulf water temperatures. Although the acute negative consequences of Red Tide exposure on pulmonary health in humans are relatively well-documented, recent studies of ER admissions during Red Tide blooms also demonstrate increased diagnoses of neurological conditions. The impact on the central nervous system of repeat exposure of brevetoxin in humans is not known, but frequent exposure to the closely-related ciguatoxin can result in chronic neurological illness including conditions similar to chronic fatigue syndrome. Furthermore, other chronically exposed mammals, like manatees and dolphins, display a wide variety of neurological signs most likely due to the known mechanism of action of brevetoxins on voltage-gated ion channels in the peripheral and central nervous systems. One of the longest Red Tide blooms on record, November 2017 to February 2019, exposed southwest Florida residents to prolonged and intense aerosolized brevetoxin levels. We have begun enrolling volunteer residents from the two-county region of Manatee and Sarasota (collectively “Manasota”) who were differentially exposed during this bloom by virtue of their home or work locations. These subjects have provided demographic, health history, and zone/activity information as well as biological samples. These subjects will be part of the cohort that we would like to follow over 18 months during periods of absence or presence of subsequent blooms. The cohort recruitment will be completed with volunteers who live in coastal regions as well as those who live further inland and who will have experienced much lower, or no, brevetoxin aerosol exposure. We will correlate their exposure to aerosolized brevetoxins with neurological diagnoses. Furthermore, we will examine biomarkers of brevetoxin exposure in relation to the same neurological sequelae. The purpose of this study is to determine how exposure relates to neurological diagnoses and to begin to characterize differences between those that develop neurological diagnoses and those that do not. For instance, exposure dose, duration, or markers of immune response may predict neurological outcomes. This work will be the first to provide longitudinal data on the neurological consequences of repeat brevetoxin exposure, generate a cohort for the examination of long-term outcomes and will establish a biorepository for studies of brevetoxin exposure and human health.