Interactions between paired homologous genes can lead to changes in gene expression. Such trans-regulatory effects exemplify transvection and are displayed by many genes in Drosophila, in which homologous chromosomes are paired somatically. Transvection involving the yellow cuticle pigmentation gene can occur by at least two mechanisms, one involving the trans-action of enhancers on a paired promoter and a second involving pairingmediated bypass of a chromatin insulator. A system was developed to evaluate whether the action of the yellow enhancers in trans could be reconstituted outside of the natural near telomeric location of the yellow gene. To this end, transgenic flies were generated that carried a yellow gene modified by the inclusion of strategically placed recognition sites for the Cre and FLP recombinases. Independent action of the recombinases produced a pair of derivative alleles, one enhancerless and the other promoterless, at each transgene location. Transvection between the derivatives was assessed by the degree of interallelic complementation. Complementation was observed at all eight sites tested. These studies demonstrate that yellow transvection can occur at multiple genomic locations and indicate that the Drosophila genome generally is permissive to enhancer action in trans. G ene expression is controlled by regulatory elements that modulate transcription in appropriate temporal and spatial patterns. In eukaryotes, these control elements often reside in large, complex regions, requiring action over long distances to elicit changes in transcription of a target promoter. In some cases, the control elements of paired homologous genes can interact in trans to alter gene expression. Such trans-regulatory effects illustrate processes known as transvection. Transvection was described first in Drosophila (1), which has homologous chromosomes that are paired somatically. Transvection and related processes have been reported in many organisms besides Drosophila (for example, refs. 2-7, and reviewed in refs. 8-11). These observations suggest that transvection may be generally possible for eukaryotic control regions and that these processes may be important for the normal regulation of some genes. For example, chromosomal pairing is proposed to play a role in gene silencing associated with imprinting and X chromosome inactivation (4, 12).In Drosophila, interactions between homologous chromosomes can have either a positive or negative effect on transcription. Examples of negative effects include repression of white gene expression by certain alleles of zeste, trans silencing conferred by the insertion of a block of heterochromatin near the brown gene, and pairing-dependent silencing, as exemplified by the effects of Polycomb response elements (reviewed in refs. 8-11, 13, and 14). Examples of positive effects include events at the Ultrabithorax, Abdominal B, decapentaplegic, yellow, and eyes absent genes (1,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).A useful system for studying the mechanisms involved in posi...