The melatonin receptors, MEL-1A-R and MEL-1B-R, are members of the superfamily of guanine nucleotide-binding regulatory protein (G protein)-coupled receptors. The melatonin receptors are activated by the hormone melatonin (Mel), which is secreted by the pineal gland at night as part of the circadian clock. MEL-1A-R, a 37 kD protein, is thought to be involved in pacing the biological clock. However, both MEL-1A-R and MEL-1B-R are implicated in controlling cellular growth in response to melatonin. MEL-1B-R is an integral membrane protein expressed in retina and less in brain and hippocampus. Functional studies of NIH/3T3 cells stably expressing the MEL-1B-R melatonin receptor indicate that it is coupled to inhibition of adenylyl cyclase.