Enzyme inhibition by fullerene derivatives has attracted much attention. In this communication, effects of two water-solube fullerene derivatives, fullerol and trimalonic acid C60 (TMA C60) on polymerase chain reaction (PCR) were investigated by using PCR of β-actin cDNA derived from HeLa cells as an experimental model. Both fullerol and TMA C60 were found to inhibit PCR in a dose-dependent manner. PCR was ultimately inhibited while the concentrations of each compound were not less than 0.01mM. In contrast, mannitol exerted no effects on PCR while its concentration increased up to 2mM. Compensation experiments with Thermus aquaticus (Taq) DNA polymerase revealed that both fullerol andTMAC60 inhibited the enzymatic activity of Taq DNA polymerase, and the inhibitory potency of TMA C60 was slightly greater than that of fullerol. Our data provides some novel aspects on the enzyme inhibiting activities of fullerene derivatives.