In neurons, arc (activity regulated, cytoskeleton associated) is an immediate early gene (IEG) that is rapidly and transiently induced by excitatory stimulation. It is believed to mediate rapid strengthening of signaling structures at activated synaptic sites. Unlike most IEGs, arc does not encode nuclear transcription factor, but an effector molecule that associates with the actin cytoskeleton. Cytoskeletal rearrangements of microtubule- and actin-based networks that occur at activated synapses also take place in similar fashion during the formation of the acrosome, the site of regulated exocytosis at fertilization. In this paper, arc is reported to be highly expressed both at the RNA and protein levels in postmeiotic germ cells in the testis of adult mice. Immunofluorescence studies reveal that arc is first present in the perinuclear region of round, elongating, and elongate spermatids, where it colocalizes with the developing acrosome. In isolated mature sperm, arc is present in the acrosomal region of the sperm head, the centriole region of the neck, and the principal piece of the tail. Arc is lost to varying degrees during sperm capacitation and in acrosome-reacted sperm. Phalloidin staining of mature sperm cells reveals an overlapping pattern of filamentous-actin and arc expression. These results support a role for arc and the actin cytoskeleton in the acrosome formation, the sperm acrosome reaction, and in sperm cell motility.