The aim of this project is to investigate the function of selected cloned genes primarily expressed in the adult nervous system of Drosophila melanogaster. To this end a reverse genetic approach of site-selected mutagenesis was undertaken. A number of genes were chosen as targets for mutagenesis and P element insertions were obtained in three genes encoding two classes of G protein alpha subunit (DGalphai and DGalphao; Provost et al., 1988; Yoon et al., 1989) and the gene encoding a catalytic subunit of cAMP-dependent protein kinase (DC0; Kalderon and Rubin, 1988). Strains containing P element insertions were homozygous viable and presented no discernable phenotype. The P element insertion in the gene encoding DGalphao (dgo) was mobilised during a secondary mutagenesis in an attempt to create deletions via imprecise P element excision. A variety of alterations were detected in the vicinity of the original P element insertion in the dgo locus by Southern analysis, but the majority of these had no phenotypic consequence. Eight lines had a recessive lethal phenotype, and four exhibit embryonic lethality. This lethal phase is consistent with a subsequent report that mutations in the dgo gene result in embryonic lethality with associated defects in the developing embryonic central nervous system (Guillen et al., 1995). Complementation analysis between the recessive lethal lines show that the mutations do not fall into the same complementation group. Two lines, 273 and 459, with embryonic lethality have had a deletion of DNA corresponding to the dgo coding region and are therefore null mutations in the dgo gene. In addition to having a mutation in the dgo gene, 273 and 459 also fail to complement two other recessive lethal mutations that map to the same chromosomal location. Similar to dgo, longitudinals lacking (lola; Seeger et al., 1993) and bumper-to-bumper (btb; Kania et al.,1995), are both required in the developing embryonic nervous system. Thus, 273 and 459 have large deletions of flanking DNA that encompass at least two additional essential loci.