Tyrosine is a precursor of melanin synthesis and might thus present a valuable marker for melanoma. The aim of this study was to evaluate the uptake of alpha-methyl-tyrosine (AMT) in melanoma cell cultures and to assess its usefulness as a radiopharmaceutical for staging melanoma patients with whole-body scintigraphy. Melanoma (M19-cell lines) and fibroblast (negative control) cell cultures were incubated with 125I-AMT and the radioactive uptake in the cell lines was measured in a gamma-counter over 24 h. For in vivo studies, planar whole-body scintigraphy and single photon emission computed tomography (SPECT) of the tumour region was performed following injection of 250-350 MBq 123I-AMT in six patients with known melanoma metastases. Findings were compared with results of whole-body positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) as a standard of reference. Fibroblasts showed an unchanged uptake of (mean +/- SD) 0.56 +/- 0.09% 15 min and 0.066 +/- 0.09% 24 h, respectively, after incubation of 125I-AMT, whereas there was an increased uptake in melanoma cell cultures over time from 0.9 +/- 0.05% to 7.5 +/- 1.6%. In staging melanoma patients, the sensitivity of whole-body AMT-scintigraphy compared with FDG-PET was 37% (10 of 27 metastases). AMT is transported and metabolized to a high extent in melanoma cells and 123I-AMT is accumulated in melanoma metastases. Owing to its low sensitivity, however, the clinical use of whole-body AMT scintigraphy cannot be recommended.