In their recent Trends in Parasitology article on tolerance and antimalarial drug resistance, Hastings and Watkins [1xTolerance is the key to understanding antimalarial drug resistance. Hastings, I.M. and Watkins, W.M. Trends Parasitol. 2006; 22: 71–77Abstract | Full Text | Full Text PDF | PubMed | Scopus (50)See all References][1] made the extremely important point that resistance is not an all-or-nothing effect, and that several mutations can occur before the malarial parasite fails to respond to the full therapeutic treatment in the patient. Clearly, this must be taken into account in any modelling on the development of resistance. The authors use the word ‘tolerance’ to describe the intermediate state between susceptibility and complete drug failure. We made the same mistake in work carried out in Kenya in the 1980s, which showed the ‘resistance’ of Schistosoma mansoni to oxamniquine in an article entitled ‘Tolerance of Kenyan Schistosoma mansoni to oxamniquine’ [2xTolerance of Kenyan Schistosoma mansoni to oxamniquine. Coles, G.C. et al. Trans. R. Soc. Trop. Med. Hyg. 1987; 81: 782–785PubMed | Scopus (33)See all References][2]. It should have been entitled ‘resistance’.To try and correct this misunderstanding, we defined resistance in Schistosoma as the following [3xDefining resistance in Schistosoma. Coles, G.C. and Kinoti, G.K. Parasitol. Today. 1997; 13: 157–158Abstract | Full Text PDF | PubMedSee all References][3]: ‘A population of Schistosoma is resistant when either a susceptible population shows a significant decrease in response to a schistosomicide or is significantly less responsive than a fully susceptible population…It is complete when the maximum dose of drug tolerated by the host has no effect on the parasite population.’ As used by Fallon et al. [4xSchistosome resistance to praziquantel: fact or artifact?. Fallon, P.G. et al. Parasitol. Today. 1996; 12: 316–320Abstract | Full Text PDF | PubMed | Scopus (60)See all References][4] and discussed in our previous letter [3xDefining resistance in Schistosoma. Coles, G.C. and Kinoti, G.K. Parasitol. Today. 1997; 13: 157–158Abstract | Full Text PDF | PubMedSee all References][3], ‘tolerance is an innate insusceptibility of a parasite to a drug, even before the parasite has been exposed to the drug.’ We cited the example of oxamniquine, which does not work against Schistosoma haematobium. Tolerance can be total or it can be stage-specific; for example, ivermectin does not kill inhibited cyathostomins in horses but is extremely effective against the lumenal stages [5xThe effect of ivermectin treatment against inhibited early third stage, late third stage and fourth stage larvae and adult stages of the cyathostomes in Shetland ponies and spontaneous expulsion of these helminths. Eysker, M. et al. Vet. Parasitol. 1992; 42: 295–302Crossref | PubMed | Scopus (43)See all References][5]. There is a similar confusion by farmers when they think anthelmintics are working adequately but low levels of resistance are detected on the farm. This low-level resistance will not necessarily show up as lost productivity but serves as a warning that future problems will develop if changes are not made in the use of that anthelmintic. This slightly lowered efficacy is not tolerance, but resistance.I believe it is important to use the same terminology when discussing drug resistance, whether it is in malaria, nematodes or any other parasites. I would, therefore, like to suggest that the definition we proposed in 1997 [3xDefining resistance in Schistosoma. Coles, G.C. and Kinoti, G.K. Parasitol. Today. 1997; 13: 157–158Abstract | Full Text PDF | PubMedSee all References][3] is adopted by all parasitologists, and that ‘tolerance’ is not used to describe intermediate levels of resistance but is confined to the innate inactivity of a drug towards a stage or a particular species of parasite, in which activity might be expected as a result of drug efficacy against a closely related species.