The temporal and spatial expression of the period gene of Drosophila melanogaster has been analyzed by examining the expression of a per beta-galactosidase fusion gene in transformants and by in situ hybridization experiments with wild-type flies. Several strains of Drosophila melanogaster, transformed with the fusion gene, have been generated. The gene is active in mid-late embryos in the midline of the nervous system. Thereafter, beta-galactosidase activity is undetectable until the pupal stage when the prothoracic gland-corpora allata and the optic lobes are beta-galactosidase positive. In adults a surprisingly large number of tissues stain positively, including antennae, proboscis, eyes, optic lobes, cells of the central brain, cells of the thoracic ganglia, gut, Malpighian tubules, and ovarian follicle cells. The temporal pattern of expression agrees well with previous estimates made from developmental Northern blots with RNA extracted from wild-type animals. We suggest that many of the tissues that express the per gene contain their own intrinsic oscillator activity.