In the 16 November Nature, Fraser et al. and Gönczy et al. present the first large-scale reverse genetic analyses of a multicellular organism (Nature 2000, 408:325-330; Nature 2000, 408:331-336). Fraser et al. use RNA-mediated interference (RNAi to target 2,416 predicted genes on chromosome I of the worm Caenorhabditis elegans by feeding the worms with bacteria expressing double-stranded RNA. Of the analyzed genes, 13.9% show a phenotype, increasing the number of sequenced chromosome I genes with a known phenotype from 70 to 378. The identified genes include 90% of known embryonic lethal genes from chromosome I, but only 45% of genes with known post-embryonic phenotypes, with genes involved in nerve and sperm cell function apparently resistant to RNAi. The majority (60%) of the phenotypes were embryonic lethal, including many genes involved in basic metabolism. The largest class of post-embryonic phenotypes are in the uncoordinated (Unc) class, which generally relate to neuromuscular function. Extrapolating from this screen, Fraser et al. estimate that the worm requires about 5,400 genes to live under standard laboratory conditions.