During metamorphosis of Manduca sexta, defined sets of neurons show a dramatic accumulation of cyclic guanosine monophosphate (cGMP). Although many of these cells show low but detectable levels of cGMP during specific developmental windows, these levels are enhanced dramatically during dissection of the central nervous system (CNS). The ability of these neurons to show this induced cGMP expression depends on the developmental stage. Larvae do not show this capacity but it appears during the transition from the larval to the pupal stage. There are two different classes of response: the early expressing neurons start to show a cGMP response at the beginning of the prepupal stage while the late expressing cGMP neurons start at different times during the pupal-adult transition. The former set includes larval neurons that will likely be remodeled during metamorphosis, and a number of them are serotonergic. The late-expressing group also includes some larval cells, but most are adult-specific neurons. At least for one adult-specific cluster, the antennal lobe neurons, the cGMP expression parallels the maturation phase of these cells.