The characteristics of the uptake of acetaminophen (N-acetyl-p-aminophenol or paracetamol, APAP) in incubations of isolated rat liver cells were consistent with diffusion of the drug being the predominant mechanism of APAP influx in these cells at concentrations above 0.5 mM. At lower substrate concentrations (below 0.5 mM) a saturable component was apparent. Both uptake processes could have a role in the control of the metabolism of APAP, because, at low concentrations, there was no intracellular accumulation of unconjugated drug, all the APAP entering the cell being converted to sulphate and glucuronide. After addition of drug, there was a lag phase of approximately 5 min before APAP-glucuronide and APAP-sulphate appeared in the incubation medium; during this time both conjugates accumulated inside the cells. These results have implications for our understanding of the mechanisms of APAP transport, and indicate how these processes may affect the drug's overall metabolism.