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Blacktip reef sharks are regularly caught by inshore fisheries and are vulnerable to depletion because of their small litter sizes and long gestation periods. Traumatogenic. May become aggressive to spear fishers and are reported to bite people wading in shallow water. Generally marketed fresh (as fillet), may be dried, salted, smoked or frozen. Fins are valued for shark-fin soup; a market that is decimating shark populations worldwide. They are also sought for their liver as source of oil.
Caribbean reef sharks are sometimes seen resting motionless on the sea floor or inside caves; it is the first active shark species in which such a behavior was reported. In 1975, Eugenie Clark investigated the famed "sleeping sharks" inside the caves at Isla Mujeres off the Yucatan Peninsula, and determined that the sharks were not actually asleep as their eyes would follow divers. Clark speculated that freshwater upwellings inside the caves might loosen parasites on the sharks and produce an enjoyable "narcotic" effect. If threatened, Caribbean reef sharks sometimes perform a threat display, in which they swim in a short, jerky fashion with frequent changes in direction and repeated, brief (1–1.2 second duration) drops of the pectoral fins. This display is less pronounced than the better-known display of the grey reef shark (C. amblyrhynchos).
Grey reef sharks are often curious about divers when they first enter the water and may approach quite closely, though they lose interest on repeat dives. They can become dangerous in the presence of food, and tend to be more aggressive if encountered in open water rather than on the reef. There have been several known attacks on spearfishers, possibly by mistake, when the shark struck at the speared fish close to the diver. This species will also attack if pursued or cornered, and divers should immediately retreat (slowly and always facing the shark) if it begins to perform a threat display. Photographing the display should not be attempted, as the flash from a camera is known to have incited at least one attack. Although of modest size, they are capable of inflicting significant damage: during one study of the threat display, a grey reef shark attacked the researchers' submersible multiple times, leaving tooth marks in the plastic windows and biting off one of the propellers. The shark consistently launched its attacks from a distance of 6 m (20 ft), which it was able to cover in a third of a second. As of 2008, the International Shark Attack File listed seven unprovoked and six provoked attacks (none of them fatal) attributable to this species.
Like many sharks, the Caribbean reef shark mainly eats bony fishes. The shark uses six keen senses to locate its prey: olfactory, visual, tactile (including water vibration sensitivity through a lateralis canal system), auditory, gustatory, and electric reception. The Caribbean reef shark is especially adapted to detecting low frequency sounds (indicative of a struggling fish nearby).