Double-stranded RNA (dsRNA) can cause specific gene silencing upon ingestion in many animals and is being developed as a pesticide to target essential genes in animal pests. However, the organismal response to ingested dsRNA that leads to eventual gene silencing within animals is unknown. In the worm C. elegans, ingested dsRNA is recruited into the RNA interference pathway by the dsRNA-binding protein RDE-4 for eventual gene silencing by Argonaute proteins. We found that when RDE-4 was expressed at high levels within a tissue, silencing by ingested dsRNA could occur in rde-4(-) somatic tissues but not in the rde-4(-) germline. Such silencing by dsRNA-derived mobile RNA had different Argonaute requirements and could escape inhibition by expressed repetitive DNA. Thus, our results suggest that, when animals ingest dsRNA, the ingested dsRNA and dsRNA-derived mobile RNAs use distinct mechanisms to silence genes. Overall design: The wild-type N2 strain was subjected to L4440 feeding RNAi (control) or bli-1 feeding RNAi in liquid culture. Total RNA was isolated from both worm cultures and subjected to poly-A-selected RNA-Seq using the Illumina HiSeq1500 platform. The coverage for each gene of interest was determined after mapping to ce6 using TopHat2.