Originally discovered in plants(1,2), the phenomenon of co-suppression by transgenic DNA has since been observed in many organisms from fungi(3) to animals(4-7): introduction of transgenic copies of a gene results in reduced expression of the transgene as well as the endogenous gene. The effect depends on sequence identity between transgene and endogenous gene. Some cases of cosuppression resemble RNA interference (the experimental silencing of genes by the introduction of double-stranded RNA)(8), as RNA seems to be both an important initiator and a target in these processes(9-13). Here we show that co-suppression in Caenorhabditis elegans is also probably mediated by RNA molecules. Both RNA interference(14,15) and co-suppression(16) have been implicated in the silencing of transposons. We now report that mutants of C. elegans that are defective in transposon silencing and RNA interference (mut-2, mut-7, mut-8 and mut-9) are in addition resistant to co-suppression. This indicates that RNA interference and co-suppression in C. elegans may be mediated at least in part by the same molecular machinery, possibly through RNA-guided degradation of messenger RNA molecules.