Fresh water cyanobacteria harmful algal blooms (HABs) are increasing in frequency and severity in the U.S. and globally. Blooms produce potent and lethal cyanotoxins which poison people and animals. This is a serious emerging “One Health” problem. Among the many cyanotoxins produced by HABs are hepatotoxic and carcinogenic microcystins. Currently, the state-of-the-art diagnostic approach for microcystin intoxications in people is measuring elevated blood serum liver enzymes as biomarkers of effect. Unfortunately, elevated liver enzymes are late biomarkers of microcystin effects. The objective of this study is to identify and characterize early biomarkers of microcystin exposure and effects in humans using the mouse model. These early biomarkers will be used for diagnosis in populations exposed to contaminated water in order to mount early intervention procedures to protect individual and public health.