We describe here a dominant mutation, night blindness b (nbb), which causes an age-related visual system defect in zebrafish. At 4-5 months of age, dark-adapted nbb1/2 mutants show abnormal visual threshold fluctuations when measured behaviorally. Light sensitizes the animals; thus early dark adaptation of nbb1/2 fish is normal. After 2 hr of dark adaptation, however, visual thresholds of nbb1/2 mutants are raised on average 2-3 log units, and rod system function is not detectable. Electroretinograms recorded from nbb1/2 mutants are normal, but ganglion cell thresholds are raised in prolonged darkness, suggesting an inner retinal defect. The visual defect of nbb1/2 mutants may be likely caused by an abnormal olfactoretinal centrifugal innervation; in nbb1/2 mutants, the olfactoretinal centrifugal projection to the retina is disrupted, and the number of retinal dopaminergic interplexiform cells is reduced. A similar visual defect as shown by nbb1/2 mutants is observed in zebrafish in which the olfactory epithelium and olfactory bulb have been ex cised. Homozygous nbb fish display an early onset neural degeneration throughout the CNS and die by 7-8 d of age.