Harmful Algal Blooms (HABs) in freshwater systems and intensified aquaculture have increased the risk to human health through exposure to cyanotoxins such as microcystin-LR (MC-LR). To understand the uptake and processing of MC-LR in humans, the pig was chosen as an animal model. This was assessed by repeated exposure for 13 weeks of eight animals dosed daily with MC-LR at 0.04 μg/kg bw, repeated with six animals over five weeks at a dose 50 times higher at 2 μg/kg bw. An analytical method was developed for MC-LR in porcine serum and also to analyse levels of free MC-LR in harvested porcine tissues, with Lemieux Oxidation employed to determine bound MC-LR in these tissues. MC-LR was not detected in the serum of treated animals from either experiment but free MC-LR was observed in the large intestine and kidney from two animals from the higher dosed group at levels of 1.4 and 1.9 μg/kg dry weight (dw) respectively. The results indicated 50% of higher dosed animals accumulated bound MC-LR in liver tissue, averaging 26.4 μg, approximately 1.1% of the dose administered. These results point to the potential uptake and accumulation of MC-LR in human liver tissue exposed chronically to sub-acute doses.