We report studies on the mechanism of action of bisphenol A (BPA) on the differentiation of oligodendrocyte precursor cells (OPCs). Our results show that: (1) BPA inhibits the differentiation of OPCs induced by exposure to thyroid hormone (T3). (2) The effect is mediated through various mechanisms via the thyroid hormone receptor (TRbeta1) which is considered to be responsible for OPC differentiation. (3) The action of BPA on OPC differentiation does not involve the FcRgamma-Fyn-myelin basic protein (MBP) cascade as an inducer of OPC differentiation nor does it suppress CREB phosphorylation, which is considered to be induced by the T3-TR complex. (4) The presence of MBP isoforms (21.5, 18.5, 17.0 and 14.0 kDa) was detected in OPCs, and the expression of exon 2-containing isoforms (i.e. 17.0 and 21.5 kDa) was upregulated upon treatment with T3. In contrast, expression of MBP was inhibited by BPA.