Murine colon 26 carcinoma growing at either subcutaneous (s.c.) or intramuscular (i.m.) inoculation sites causes cachexia in mice. Such animals show extensive loss of body weight, wasting of the muscle and adipose tissues, hypoglycaemia, and hypercalcaemia, even when the tumour weight comprises only about 1.9% of carcass weight. In contrast, the same tumour when inoculated into the liver does not cause any sign of tumour-related cachexia even when the tumour becomes much larger (6.6% of carcass weight). Interleukin 6 (IL-6), a mediator associated with cachexia in this tumour model, is detected at high levels both in the tumour tissues and in the circulating blood of mice bearing colon 26 tumour at the s.c. inoculation site. In contrast, only minute levels of IL-6 are detected in the tumour grown in the liver. The colon 26 tumour grown in the liver does not lose its ability to cause cachexia, because the tumour when re-inoculated s.c. is able to cause extensive weight loss and produce IL-6 as did the original colon 26 cell line. Histological studies revealed differences in the composition of tumour tissues: the tumours grown in the subcutis consist of many polygonal tumour cells, extended-intercellular space, and high vascular density, whereas those grown in the liver consist of spindle-shaped tumour cells. Thus, the environment where tumour cells grow would be a critical factor in determining the cachectic phenotype of cancer cells, including their ability to produce IL-6.