Using quantitative bioluminescence imaging, tissue concentrations of ATP, glucose, and lactate were registered in biopsies that were taken from primary tumors of human head and neck at the time of first cancer diagnosis. From 15 patients investigated at present, 6 had locoregional lymph node metastasis, 6 had no detectable metastatic spread, 2 biopsies contained dysplasias, and 1 biopsy consisted exclusively of normal mucosal and submucosal tissue. There was no correlation between staging or grading and any of the metabolic parameters measured. Mean lactate concentrations (+/-SD) were significantly higher and scattered over a wider range in tumors with metastatic spread (12.3 +/- 3.3 mumol/g) in comparison with malignancies in patients without metastasis (4.7 +/- 1.5 mumol/g). Despite the low number of patients, these differences were statistically highly significant (P < 0.005; Mann-Whitney). Neither ATP nor glucose contents showed such a correlation with the emergence of metastasis. Mean lactate contents of the two dysplasias were 0.1 and 3.5 mumol/g; that of the normal tissue was 0.1 mumol/g. Although these findings have to be verified in a higher number of patients, the present data indicate that elevated lactate levels in primary tumors of head and neck may be associated with a high risk of metastatic spread. With the underlying mechanisms remaining to the investigated, lactate imaging is possibly useful as an early indicator of the malignant potential of tumors in patients.