At external concentrations of 50,UM, L-methionine was rapidly taken up by hepatocytes, whereas almost no S-adenosylmethionine (SAM) was removed from the incubation medium. SAM did not enter the intracellular water space but equilibrated with a very small pool, which was most likely to be situated on the external side of the plasma membrane. Methyl groups from external L-methionine, but not from external SAM, were incorporated into total and nuclear RNA. A significant incorporation of methyl groups into phospholipids occurred not only with methionine but also with SAM. After subfractionation of hepatocytes it became evident that methyl groups from SAM were mainly incorporated into plasma-membrane phospholipids, and that phospholipid methylation in other cellular compartments resulted from contamination with plasma membrane. The pattern of methylation of the various phospholipid species with SAM as precursor was different from that obtained with L-methionine. In contrast with external L-methionine, external SAM did not enter the intracellular SAM pool. According to these results a transport system for SAM does not exist in rat hepatocytes, although methyl groups from external SAM can phospholipids from the outside.Studies concerning transmethylation processes in intact cells or tissues can be done by using [Me-3H]or [Me-14C1-methionine. After entering the cell the labelled methionine is converted into the corresponding labelled SAM, which then mixes with the internal pool of unlabelled SAM. From this pool methyl groups are transferred by specific methyltransferases on to their physiological acceptors.Since the early experiments of Stekol et al. (1958), who observed an increased formation of methylated products by rat liver slices in the presence of exogenous SAM, various groups have looked for a specific uptake system for SAM. This would offer the opportunity to label the internal SAM pool directly and allow measurements of transfer of methyl groups on to proteins without interference Abbreviations used: Hepes, 4-(2-hydroxyethyl)l-piperazine-ethanesulphonic acid; PtdEtn, phosphatidylmonoethanolamine; Ptd[EtnI2, phosphatidyldiethanolamine; PtdCho, phosphatidylcholine; SAM, S-adenosyl-L-methionine; SDS, sodium dodecyl sulphate.be incorporated into plasma-membrane with the incorporation of labelled methionine via protein synthesis.An uptake system for SAM has indeed been described for yeast cells by Svihla & Schlenk (1960) and by Spence (1971) and was characterized by Murphy & Spence (1972). The transport was temperature-and energy-dependent, had an apparent Km for SAM of 3.3,pM and was inhibited by S-adenosylhomocysteine and S-adenosylethionine. Similar findings were obtained by Nakamura & Schlenk (1974). Stramentinoli et al. (1978a,b) found a transport system for SAM in rabbit erythrocytes. Zappia et al. (1978) described the transport of exogenous SAM into isolated perfused rat livers, and Stramentinoli et al. (1978) claimed even that exogenous SAM was able to protect rat livers against galactosamineinduced liver...