Mercury (Hg) is a global concern of human health, as the consumption of fish and shellfish through methylmercury (MeHg) bioaccumulation could expose human being to health risk. In addition to this aquatic food chain pathway, recently, considerable levels of MeHg have been found in rice, particularly in contaminated areas, and thus rice consumption could act as another major pathway for human exposure to MeHg. The occurrence of elevated levels of MeHg in rice may suggest that rice products, such as infant rice cereals, could contain the MeHg being transferred from the rice used during the manufacture processes. Analysis of infant cereals commonly marketed in the United States and China suggests that some rice cereals do contain elevated levels of MeHg and total Hg (THg), posing potential health risks as infants could consume rice cereals as a major fraction of their diets. For a more accurate evaluation of the potential health risks to infants caused by consumption of rice cereals, the bioaccessibility of MeHg in the rice cereals was assessed using physiologically based extraction methods. An in vitro gastrointestinal extraction method was employed to determine the bioaccessibility of MeHg in rice-based infant cereals and to examine the factors controlling the MeHg bioaccessibility. The fractions of MeHg in infant cereals extracted into the dissolved phase (digestive juice) by simulated gastrointestinal fluids ranged from 25% to 74%. However, it seems that MeHg, even after being released from the solid matrices, could be re-adsorbed onto the undigested sample residues during the course of extraction, which may obstruct the accurate evaluation of the bioaccessibility of MeHg in the samples. For the purpose of comparison, fish samples were extracted using the same in vitro method to evaluate the bioaccessibility of MeHg in fish. The results may suggest that care should be exercised when using in vitro physiologically based extraction tests to assess the bioaccessibility of MeHg in food sources and solid matrices in general.