We compared two melanoma-specific radioiodine labeled compounds 4-(3-dimethylaminopropylamino)-7-iodoquinoline (I) and L-3-iodo-alpha-methyltyrosine (IV) using three hamster groups. Two groups consisted of hamsters with subcutaneous or subscleral melanotic melanoma, and the third had healthy animals as controls. For the chosen tumor model and in comparison with the quinoline derivative (I), the tyrosine derivative (IV) proved to have some better properties as a melanoma-specific radio-pharmaceutical. This result holds for the first 24 h after administration, thus recommending (IV) for the 123I label. While in that time period (I) did not sufficiently accumulate in the melanoma to compete with the high background activities, especially in the abdominal organs, (IV) had its highest tumor concentration 1 h after administration. The derivative (IV) cleared more slowly from the tumor tissue than from the other organs thus increasing the tumor-to-organ ratio. There was no obvious difference in the biodistribution of (I) and (IV) in relation to the site of the melanoma growth, i.e. eyes and skin. Generally, all three groups of hamsters exhibited similar accumulation and clearance characteristics for each radiopharmaceutical. In contrast to (I), which took part in the formation of the biopolymer melanin, (IV) acted as a reversible inhibitor of the enzyme tyrosine hydroxylase. The affinity to the tyrosine hydroxylase and not the function as a melanin precursor lead to an accumulation of (IV) in the melanoma tissue.