Most flatfish have a white lower blind side and a brown or grey upper ocular side which can display cryptic patterning with dark areas and white spots. Active predatory flatfish likeReinbardtius hippoglossoideshave complete ambicoloration and this can also occur partly or completely in other flatfish such asPleuronectes americanus.Both hypermelanosis and hypomelanosis can occur in aquacultured flatfish. Dermal and epidermal melanophores, xanthophores and iridophores occur in various flatfish species and patterning has a morphological basis with differences in the size and frequency of chromatophores. The patterning is also physiological displaying differential responsiveness to background and stress. InPleuronectes americanuschromatic decentralization and hypophysectomy demonstrate that the pattern‐related responsiveness of melanophores is neurally controlled and that xanthophores are regulated by the pituitary.In vitropharmacology indicates that α‐adrenoceptors mediate melansome aggregation and β2‐adrenoceptors mediate dispersion. There is a pattern‐related differential balance in a and β‐adrenoceptor sensitivity but experiments after chemical sympathectomy suggest the additional participation of modulatory factors.