The brain of larval Rhodnius prolixus releases neurohormones with a circadian rhythm, indicating that a clock system exists in the larval brain. Larvae also possess a circadian locomotor rhythm. The present paper is a detailed analysis of the distribution and axonal projections of circadian clock cells in the brain of the fifth larval instar. Clock cells are identified as neurons that exhibit circadian cycling of both PER and TIM proteins. A group of eight lateral clock neurons (LNs) in the proximal optic lobe also contain pigment-dispersing factor (PDF) throughout their axons, enabling their detailed projections to be traced. LNs project to the accessory medulla and thence laterally toward the compound eye and medially into a massive area of arborizations in the anterior protocerebrum. Fine branches radiate from this area to most of the protocerebrum. A second group of clock cells (dorsal neurons [DNs]), situated in the posterior dorsal protocerebrum, are devoid of PDF. The DNs receive two fine axons from the LNs, indicating that clock cells throughout the brain are integrated into a timing network. Two axons of the LNs cross the midline, presumably coordinating the clock networks of left and right sides. The neuroarchitecture of this timing system is much more elaborate than any previously described for a larval insect and is very similar to those described in adult insects. This is the first report that an insect timing system regulates rhythmicity in both the endocrine system and behavior, implying extensive functional parallels with the mammalian suprachiasmatic nucleus. J. Comp. Neurol. 518:1264 -1282, 2010. INDEXING TERMS: insect; clock; lateral neurons; PDF; neuroarchitecture; timing network; PERIOD; TIMELESS Circadian timing systems have been found in all organisms that have been studied, from bacteria to humans. They enable organisms to anticipate the arrival of favorable times of day (or seasons of the year) for execution of diverse rhythmic activities ranging from gene expression to hormone secretion, growth, reproduction, and behaviours. These circadian rhythms are driven by endogenous biological clocks centered primarily in groups of nerve cells. These cells generate rhythms with a periodicity of about 24 hours that become synchronized (entrained) to the precisely 24-hour external world by time signals (Zeitgebers) arising principally from components of the light/ dark cycle, such as dusk and dawn.The molecular machinery with which cells generate circadian rhythmicity was first elucidated in the fruit fly, Drosophila melanogaster. Several genes have been found that are central to the generation of circadian oscillations. These oscillations fundamentally comprise feedback loops between transcription of the genes and their protein products (reviewed by Hall, 2005;Taghert and Lin, 2005) and summarized by Nitabach and Taghert (2008) and Dubruille and Emery (2008). Rhythmic transcription of the canonical clock genes in Drosophila, period (per), and timeless (tim) leads to rhythmic formation of PE...