The increase in commercial production and inevitable release of fullerenes into the environment accelerates concerns about their potential toxicity. Furthermore, the concomitant release of xenobiotics poses a health hazard to humans, and might present potential long-term risks to human health. In the present study, we found that an aqueous suspension of buckminsterfullerene (aqu-nC60) does not result in the induction of ethoxyresorufin-O-deethylase (EROD) activity in H4IIE rat liver cells in vitro. The simultaneous and sequential exposure of aqu-nC60 and the dioxin TCDD induces EROD activity to the same extent as TCDD alone (i.e. in the absence of fullerene), in spite of the high affinity of C60 for TCDD. However, the co-exposure of aqu-nC60 and PCB 126 induces elevated EROD activity, and sequential exposure increases responses 2-fold compared to the control samples. Our in vitro observations suggest a potential source of drug-drug type interaction of fullerene with xenobiotics, particularly after a sequential exposure.