Observations are presented to show that resistance to difenacoum, a rodenticide commonly used for the control of warfarin-resistant rodents, is widespread in populations of the Norway rat, Rattus norvegicus, in an area centred in north-east Hampshire. Of 202 rats trapped on 42 farms in this district and tested in the laboratory, 85% were resistant to warfarin and 14% were resistant to difenacoum. Only rats that were resistant to warfarin showed difenacoum resistance, indicating it to be a form of cross resistance. The difenacoum-resistant rats survived a dose of difenacoum that was lethal to more than 99% of susceptibles, but succumbed when this dose was increased fivefold. The results of four treatments carried out with difenacoum on farms illustrate that this level of resistance seriously reduces the effectiveness of difenacoum as a rodenticide in the field.