Chinese hamster ovary (CHO-9) and HeLa MR cells lack detectable amounts of O6-alkylguanine DNA alkyltransferase (phenotypically Mex-) and are hypersensitive to the toxic effect of N-hydroxyethyl-N-chloroethylnitrosourea (HeCNU), as compared to Mex+ derivatives. Microinjection of size-fractionated polyA+ mRNA extracted from HeLa S3 (Mex+) into CHO-9 and HeLa MR cells, or from ataxia telangiectasia (Mex+) into HeLa MR cells, gave rise to an increase in survival following treatment with toxic doses of HeCNU. Transient complementation of the Mex- phenotype was achieved with an RNA population 0.8-1 kb in size.