Adenosine deaminases that act on RNA (ADARs) convert adenosines to inosines in highly base-paired RNA. When these RNA editing enzymes target codons, the amino acid specified by the codon is often changed. Thus, ADARs create diversity by allowing more than one protein isoform to be synthesized from a single mRNA. Many of the mRNAs targeted by ADARs code for proteins involved in neurotransmission, and our goal is to correlate specific RNA editing events with specific behaviors. Given its well-characterized and relatively simple nervous system, C. elegans seems ideal for such studies. We determined that there are two ADARs in C. elegans ,
adr-1 and
adr-2 . Expression of GFP by the
adr-1 promoter indicates that
adr-1 is expressed in most cells of the nervous system as well as in the vulva, during morphogenesis. We obtained deletions in the two ADAR genes, designated
adr-1(
gv6) at the H15N14.1a/b locus and
adr-2(
gv42) at the T20H4.4 locus. Strains homozygous for the single or double deletions are viable, exhibiting subtle but interesting phenotypes that correlate with the observed expression patterns. For example, a small percentage (7%) of double mutants have a protruding-vulva phenotype (Pvl), usually associated with an improperly formed gonad. We also analyzed the function of two chemosensory neurons, the AWA and AWC neurons, which are involved in the detection of volatile chemicals. When compared to wild-type animals,
adr-1;
adr-2 double mutants tracked poorly to chemicals detected by the AWA and AWC neurons, showing consistently lower chemotaxis indices. Incubation of synthetic dsRNA with extracts from the two knockout strains reveals diminished deaminase activity in the
adr-1(
gv6) strain and a complete lack of activity in the
adr-2(
gv42) strain. Examination of known editing sites within endogenous ADAR substrates confirms these results. RNA isolated from
adr-2(
gv42) worms is completely unedited at every site examined. Interestingly, the
adr-1(
gv6) deletion affects editing sites in three ways: some sites are edited normally, some sites show decreased editing, and some sites show increased editing. Our results illustrate the importance of RNA editing for normal development and behavior in C. elegans , and set the stage for correlating specific editing events with specific behaviors.