Toxic effects on the central nervous system have been reported in patients treated with fluoropyrimidines for cancer. In the present study we have investigated the earliest effects of these drugs at the cellular level using slices of hippocampal cortex maintained in vitro. Doxyfluridine (5'-dFUrd; 50 mg/l and 500 mg/l) caused a dose dependent, reversible depression of neuronal activity. The main effect was on the pyramidal cells (population spike reduced by 14 and 25% respectively) and the afferent unmyelinated fibres (afferent fibre volley reduced by 7 and 12% respectively). Excitatory synaptic transmission was affected only by the highest concentration (field-EPSP reduced by 10%). 5-FU caused similar but less marked changes. The drugs did not cause epileptiform activity.