Human liver is enriched with CD8CT- and CD3CCD56C natural T (NT)-lymphocytes, important anti-tumour effectors, similar to murine NKTs. IL-12 promotes anti-tumour functions of NKTs. We quantified IL-12 and CD56C/CD8CT lymphocytes in normal and tumour bearing liver. We also examined the effect of IL-12 on the expansion/activation of peripheral blood cells in vitro. IL-12 was detected in normal (n ¼ 13, median 2032 pg/100 mg protein) and increased in tumour bearing liver (n ¼ 9, 3678 pg, p!0:01). Infiltrating monocytes appear to be the principal producers. Culture with IL-12 selectively expanded CD8CT and CD3CCD56CNT cells and polarised their cytokine responses to Th1-type. However, there was no in vivo expansion of these cells in tumour bearing liver. Changes observed in culture required addition of IL-2. We therefore quantified IL-2 in hepatic tissue. IL-2 was detected in normal liver (median 4700 pg/100 mg protein). Surprisingly, there was no increase in tumour-infiltrated liver (4910 pg). The presence of IL-12 may create an environment in healthy liver that promotes the accumulation of CD8CT and CD56CNT cells. Therefore, the development of metastases in the presence of high levels of IL-12 may be due to an insufficient IL-12 response. Alternatively, lack of IL-2 rather than a defect in IL-12, may be responsible for insufficient expansion/activation of tumour specific cytotoxic T lymphocytes.