Stable transfectants of Hela cells were isolated which expressed either the full-length 540-amino-acid Sindbis virus (SV) nonstructural protein, nsP1 (the form encoded by the mutant, SV(LM21)), or one of four forms with a carboxyl-terminal deletion. SV(LM21), in contrast to standard SV (SV(STD)), can replicate in Hela cells maintained in low-methionine (LM) medium. Expression of full-length nsP1(1-540), nsP1(1-492), or nsP1(1-448) resulted in complementation of SV(STD) when infected Hela cells were kept in LM medium after infection. In contrast, when cells were infected with SV(LM21) and maintained in LM medium, stable expression of any of the deleted forms of nsP1 interfered with the replication of virus. The ability of "cellular" nsP1 to complement SV(STD) in LM medium correlated with its methyltransferase activity.