We have isolated a new Drosophila mutant, satori (sat), the males of which do not court or copulate with female flies. The sat mutation comaps with fruitless (fru) at 91B and does not rescue the bisexual phenotype of fru, indicating that sat is allelic to fru (frusae). The frusat adult males lack a male-specific muscle, the muscle of Lawrence, as do adult males with otherfru alleles. A powerful approach to investigating the biological basis of sexual orientation is to use animal models that allow experimental manipulation of complex behavior. Drosophila melanogaster provides the combination of identified neurons of known projection, the applicability of classic genetic theory, and the potential for advanced molecular biological analysis, making it an excellent organism for investigating higher neural functions such as sexual orientation (1-4). We have screened about 2000 fly lines with single P-element insertions for altered sexual behavior, yielding a mutant named satori (sat; nirvana in Japanese), the males of which do not court or copulate with females. Instead, sat males exhibit homosexual courtship. We report here that sat is allelic to fruitless (fru) whose dysfunction is known to lead to "bisexual" behavior (5-7) and loss of a male-specific muscle, the muscle of Lawrence (MOL) (8,9). We further show that frusat is a likely transformer (tra) target, encodes a putative transcription factor with a BTB domain (10) and two zinc finger motifs, and is expressed in a subset of cells in the central nervous system. PlwB element as a mutator and the P (ry+A2-3) transposon as a jump starter. All flies used in the mutagenesis had a white-(w-) background, whereas the PlwB element carried a copy of w+, allowing us to recover chromosomes with PlwB insertions by selecting individuals with nonwhite eye color. After establishing fly lines with new insertions, homozygous virgin males and females were collected at eclosion, placed singly in food vials, and aged for 3 days. For behavior screening, single male and female pairs were introduced into disposable plastic syringes (volume, 1 cm3). At least 10 pairs per strain were visually observed for 1 h, and the time to copulation, duration of copulation, and percentage of pairs copulating were recorded. In this screen, we isolated seven mutations, sat, croaker (cro) (11), fickle, okina, spinster (7), chaste, and lingerer (see ref. 4 for further details of these mutations). By introducing the P (ry+A2-3) chromosome to the sat line, the mutator element was remobilized, resulting in approximately 50 lines with white eyes. sat15 and satr2 are representative of these lines: sat15 is lethal when expressed homozygously and induces mutant phenotypes when expressed heterozygously with sat, whereas sat'2 does not induce mutant phenotypes. We consider satr2 to be a revertant because precise excision of the