We isolated two cDNAs that encode isoforms of agrin, the basal iamina protein that mediates the motor neuron-induced aggregation of acetylcholine receptors on muscle fibers at the neuromuscular junction. Both proteins are the result of alternative splicing of the product of the agrin gene, but, unlike agrin, they are inactive in standard acetylchoiine receptor aggregation assays. They lack one (agrin-related protein 1) or two (agrinrelated protein 2) regions in agrin that are required for its activity. Expression studies provide evidence that both proteins are present in the nervous system and muscle and that, in muscle, myofibersand Schwann cellssynthesize the agrin-related proteins while the axon terminals of motor neurons are the sole source of agrin.