Diarrhoea and soiling of the breech with faeces ('winter scours') is a serious problem in adult Merino sheep grazing improved pastures in south-eastern Australia during winter and spring. This occurs even on farms where gastro-intestinal nematodes are effectively controlled. It was shown that winter scours was associated with the ingestion of trichostrongylid larvae, and that host factors were important in determining susceptibility to this syndrome. No differences were detected in the protective immune response of affected and unaffected sheep to gut nematodes. However, affected sheep had a hypersensitive inflammatory reaction in the pylorus and upper jejunum, characterised by the infiltration of significantly more eosinophils and changed lymphocyte populations. The changes in the lymphocyte populations included a reduced number of CD8+ cells, increased CD4+:CD8+ T-cell ratio, and significantly reduced numbers of cells reacting to interferon-gamma. High doses of infective larvae (20,000/week of Ostertagia circumcincta and Trichostrongylus vitrinus) did not induce diarrhoea in sheep not susceptible to winter scours. In contrast, only low doses (2000/week) initiated scouring in sheep selected as being susceptible to winter scours. Therefore, even considerably improved worm control programmes, including the selection of sheep with increased resistance to gut nematodes, will not prevent winter scours. Rather, phenotypic culling and genetic selection, to remove sheep susceptible to the hypersensitivity inflammatory response, is proposed as the most suitable long-term control strategy.