The complex pathogen–host–vector system of the tick-borne louping-ill virus causes economic losses to sheep and red grouse in upland United Kingdom. This paper examines the spatial distribution, incidence and effect of control measures on louping-ill virus in the Bowland Fells of Lancashire. Seroprevalence in sheep at the beginning of the study varied within the area and was affected significantly by the frequency of acaricide treatment. There was a clear decrease over 5 years in the effective force of infection on farms implementing a vaccination programme, irrespective of acaricide treatment regime, however, only one third of farms apparently eliminated infection. On farms where vaccination did not occur or where vaccination was carried out intermittently, the estimated force of infection was variable or possibly increased. Thus, as befits a complex host–pathogen system, reductions in prevalence were not as dramatic as predicted; we discuss the potential explanations for these observations.