Dreams and drug-induced hallucinations have several phenomenological similarities, especially with respect to their visual and emotive components. This similarity is hypothesized to be due to a neurochemical mechanism which is common to both states: the inactivation of the brain serotonin system. This is supported by electrophysiological data indicating that the activity of serotonin-containing neurons is depressed during both dreaming (in REM and non-REM sleep) and in response to hallucinogenic drugs. Further support for the hypothesis derives from neuropharmacological data demonstrating that decreases in synaptic serotonin are associated with increased hallucinatory-like behavior or hallucinatory experience during waking, and increased duration of REM periods during sleep. Reciprocally, increases in synaptic serotonin are associated with decreased hallucinatory-like behavior or hallucinatory experience, and with decreased REM sleep time and dream reports. Neuroanatomical evidence that serotonin is heavily concentrated in brain areas which mediate visual perception and emotive experience is consonant with the strong visual and emotive components of dreams and hallucinations. When these data are considered in conjunction with the exclusively inhibitory synaptic action of serotonin in the forebrain, an explicit hypothesis can be formulated: A cessation, or decrease, in the discharge rate of serotonin-containing neurons, either spontaneously during REM and non-REM sleep, or in response to drugs such as LSD, precipitates, through disinhibition, a dramatic increase in activity of their target neurons in brain areas mediating visual sensation and emotional experience. These latter neural events are a primary physiological substrate for the emergence of strong sensory and emotive processes during dreams and drug-induced hallucinations. © 1978.