There is accumulating evidence indicating that the presence of malignant disease is accompanied by profound changes of liver metabolism in the cancer-bearing host. We previously reported [P. C. Dagnelie, J. D. Bell, -S. C. R. Williams, T. E. Bates, P. D. Abel and C. S. Foster, Br. J. Cancer 67, 1303-1309 (1993)] marked (31)P MRS-detected alterations in phosphorylation status as well as in phospholipid and glucose metabolism in the liver of rats bearing Dunning prostate tumours. The aim of the present study was first to define abnormalities in liver metabolism in patients with a distant malignancy using (31)P MRS, and second to explore the value of including long-TR sequences in clinical (31)P MRS studies of the liver. Liver metabolite levels were expressed relative to total MR-detectable phosphate. In weight-losing (WL, n = 10), but not in weight-stable (WS, n = 13) cancer patients, liver phosphomonoester (PME) levels were significantly elevated, whereas phosphodiester (PDE) levels were reduced when compared with age-matched healthy subjects (n = 12). The TR 20:1 s ratio of PDE was increased in WS and WL cancer patients, suggesting longer T(1). At TR 20 s, but not at TR 1 s, ATP levels were significantly reduced in in WS and WL cancer patients compared with healthy subjects; similarly, P(i) levels were reduced in WL patients at TR 20 and 5s, but not at TR 1 s. ATP:P(i) ratios were unchanged regardless of TR. pH values increased in the order: healthy < cancer-WS < cancer-WL. The PME chemical shift had significantly moved downfield in cancer patients, reflecting increased contributions from glycolytic/gluconeogenic intermediates. The observed changes in PME are consistent with previous reports suggesting increased gluconeogenesis in the liver of patients with a distant malignant tumour. Furthermore, our data support the use of including long-TR sequences in clinical (31)P MRS liver studies.