Tumor accumulation of S-adenosyl-L-[methyl-11C]methionine ([11C]SAM) was investigated in mice bearing mammary carcinoma (FM3A) and in rats bearing ascitic hepatoma (AH109A). After injection of [11C]SAM the blood clearance of 11C radioactivity was rapid. The 11C level was relatively high in both tumors. The uptake ratios of tumor to organ increased with time in several organs, especially in brain and muscle. In FM3A tumor tissue the 11C was incorporated with time into the acid-precipitable fraction and 38% of the 11C was detected in this fraction at 60 min after injection. This fraction reflects the amount of 11C-methyl group transferred into macromolecules in tumor tissue. In AH109A-bearing rats the metabolisms of [11C]SAM and L-[methyl-11C]methionine ([11C]Met), in vivo precursor of SAM, were compared. Tumor uptake of [11C]SAM was about two thirds of that of [11C]Met at 20 min after injection. At this time, for the [11C]SAM 27 and 8% of the 11C in the AH109A tissue were detected in the acid-precipitable and the lipid fractions, respectively. The corresponding figures for [11C]Met were 61% and 2%. In the liver considerable amounts of 11C were observed in the lipid fraction for both tracers. These results show that [11C]SAM has potential as a tracer for tumor localization with positron emission tomography (PET) and suggest that in tumor studies combining [11C]Met and PET, it should be taken into account that the 11C-labeled methyl group of [11C]Met is not only incorporated into protein but also other macromolecules and lipids via [11C]SAM.