Two genes (ace-1 and ace-2) control the activity of five isozymic forms of the synaptically active enzyme acetylcholinesterase (AChE) in the nematode Caenorhabditis elegans. Mutants with defects in either of these genes are behaviorally and developmentally normal, but the double mutant, which has only 2% of the wild type AChE activity, has an uncoordianted (Unc) phenotype characterized by a hypercontraction and temporary paralysis of the musculature induced by mechanosensory stimuli. Genetic, behavioral, and biochemical studies suggest that at least two genetically distinct forms of AChE function in the same synapses or neuromuscular junctions. Stains for AChE in whole mounts of wild type and AChE deficient mutants are consistent with this interpretation. We are isolating additional AChE mutants which will be characterized behaviorally, genetically, histochemically, biochemically, and ultrastructurally. These mutants will be useful for establishing the molecular and subunit structure of isozymic forms of AChE; the control of AChE activity, synthesis, and localization; and the role of AChE in the development and maintenance of the extremely simple nervous system of C. elegans. We have used an ace-2 mutant specific developmental defect induced by the AChE inhibitor Aldicarb to isolate revertants of X ace-1 ace-2 double mutants. Some of these revertants may harbor defects in other components of synapses, such as the acetylcholine receptor. We have recently found evidence for two classes of acetylcholine receptors in wild type extracts. We plan to characterize the AChE mutants and the Aldicarb resistant mutants for possible alterations in the amounts and/or properties of these receptors. The identification of receptor and other synapse defective mutants will help us to understand the role of identified synaptic components in the development and maintenance of the nervous system.