We have determined the positions and sequences of 31 dominant mutations affecting a C. elegans muscle myosin heavy chain gene. These mutations alter thick filament structure in heterozygotes by interfering with the ability of wild-type myosin to assemble into stable thick filaments. These assembly-disruptive mutations are missense alleles affecting the globular head of myosin. The most strongly dominant alleles alter highly conserved residues of the myosin ATP binding site, indicating that functions of the myosin ATPase are important for thick filament assembly. Other alleles alter the site at which myosin binds actin.