A natural genetic variant in Drosophila melanogaster with a highly tissue specific effect on the level of an enzyme (aldehyde oxidase) is described. This variant causes overproduction of the enzyme by a factor of 2- to 3-fold in paragonia (male accessory sex glands) while having no significant effect on the enzyme level in other tissues. This difference is controlled by a single genetic element in the vicinity of the aldehyde oxidase structural gene that operates in a strictly cis-active mode. It is not associated with any change in enzyme primary structure detectable by a variety of physical, chemical and immunochemical tests. The most likely explanation for all of these observations is that the variant defines a cis-active regulatory element adjacent to the structural site.