C57BL/6N mice bearing Lewis lung tumours were treated with anti-gamma-interferon (IFN-gamma) monoclonal antibodies. Early, but not late, treatment inhibited tumour growth, suggesting that endogenous IFN-gamma promotes initial tumour cell proliferation. Tumour development was associated with failure to gain weight or with progressive weight loss. Anti-IFN-gamma given early or late counteracted this wasting syndrome, which indicates that IFN-gamma production subsists during tumour growth and is directly or indirectly responsible for tumour-associated cachexia. Studies of body composition in cachectic mice revealed fat tissue to be particularly affected. Fat loss was enhanced by IFN-gamma and antagonised by anti-IFN-gamma. Tumour-bearing mice were also hypersensitive to the lethal effect of endotoxin; anti-IFN-gamma was unable to mitigate this sensitisation, suggesting that IFN-gamma does not exert its cachexia-inducing effect through augmentation of the host response to an endogenous endotoxin source.