Hydrogen peroxide has been the only medicine used to treat salmon infected with sea lice [Lepeophtheirus salmonis (Krøyer)] on many farms in Scotland since 1992 and reports have suggested reduced treatment efficacy. The present study tests the sensitivity of sea lice to exposure to hydrogen peroxide under farm conditions and also in vivo by comparing lice from a farm with suspected resistance and lice from a farm that had not been pre-exposed to hydrogen peroxide. In bin treatments on fish from a farm treated with hydrogen peroxide on 41 occasions, numbers of ovigerous lice declined by only 15% and 16% in two replicates and other mobile stages by 25%. Where hydrogen peroxide had not been used, ovigerous females declined by 90% and 87% and other mobile lice stages by 97% and 99%. These trials and observed poor efficacy of cage treatments, for example only 7.5% reduction in lice numbers when fish were treated with 2000 p.p.m. for 20 mins, indicated resistance of lice to hydrogen peroxide. The mechanisms involved in the development of resistance, possible genetic selection for lice with reduced carapace permeability or detoxifying enzymes such as catalase, or tolerance through induction by subtherapeutic exposure are reviewed. Implications for lice control strategies relying on hydrogen peroxide are discussed.