Recently, several laboratories have described proteins of yeasts, mammals and Drosophila melanogaster that are 35 to 55% identical to conventional actins, but, as yet, little is known about their functions. We have initiated a systematic study by using degenerate oligonucleotides specifying two highly conserved nucleotide-binding peptides of actin, in conjunction with polymerase chain reaction techniques, to isolate Drosophila genes that encode actin-related proteins. Here we summarize the isolation of four such genes and compare the sequences of the proteins that they encode. Computer searches of databases revealed that three of the encoded proteins are homologs of yeast or mammalian actin-related proteins, implying that the corresponding proteins participate in functions common to many cell types. The fourth gene encodes a novel protein that, apparently is expressed within testes. The four genes are located within the 14D, 53D, 66B and 87C subdivisions of polytene chromosomes.