Foot-and-mouth disease (FMD) remains the single most important constraint to international trade in live animals and animal products. The factors which regulate the pathogenesis and persistence of foot-and-mouth disease virus (FMDV) are poorly understood. mRNA levels of the inflammatory cytokines interleukin (IL)-1alpha, tumour necrosis factor (TNF)-alpha and the antiviral cytokines interferon (IFN)-alpha, beta and gamma in microdissected epithelium from cattle acutely infected with FMDV O UKG 34/2001 were quantified using laser microdissection in combination with a quantitative reverse transcription polymerase chain reaction assay. Cytokine mRNA responses in microdissected epithelia from the bovine tongue, coronary band and dorsal soft palate during the acute stage of FMDV infection were different. Significantly increased expression of cytokine mRNA was found in microdissected epithelia from the coronary band and tongue of FMDV-infected cattle and the extent of cytokine mRNA induction correlated with viral RNA loads. The results suggest that epithelia from different sites of an infected animal may mount different defences following infection and this may contribute to differences in their relative capacities to clear the virus.