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It was once thought that dogs and gray wolves did not voluntarily interbreed in the wild, though they can produce fertile wolf-dog offspring. In 2010, a study of 74 Italian wolf male lineages found that 5 of them originated from dog ancestry, indicating that female wolves will breed with stray male dogs in the wild. In North America, black colored wolves acquired their coloration from wolf-dog hybridization, which occurred 10,000–15,000 years ago.Like pure wolves, hybrids breed once annually, though their mating season occurs three months earlier, with pups mostly being born in the winter period, thus lessening their chances of survival. However, one genetic study undertaken in the Caucasus Mountains showed that as many as 10% of dogs in the area, including livestock guardian dogs, are first generation hybrids. The captive breeding of wolf-dog hybrids has proliferated in the USA, with 300,000 such animals being present there.

The gray wolf has interbred extensively with the eastern wolf producing a hybrid population termed Great Lakes boreal wolves. Unlike the red and eastern wolf, the gray wolf does not readily interbreed with coyotes.Nevertheless, coyote genetic markers have been found in some wild isolated gray wolf populations in the southern United States. Gray wolf Y-chromosomes have also been found in Texan coyote haplotypes. In tests performed on a Texan canid of ambiguous species, mtDNA analysis showed that it was a coyote, though subsequent tests revealed that it was a coyote–gray wolf hybrid sired by a male Mexican gray wolf.

In 2013, a captive breeding experiment in Utah between gray wolves and western coyotes produced six hybrids through artificial insemination, making this the very first hybridization case between pure coyotes and northwestern gray wolves. At six months of age, the hybrids were closely monitored and were shown to display both physical and behavioral characteristics from both species. Although hybridization between wolves and golden jackals has never been observed, evidence of such occurrences was discovered through mtDNA analysis on jackals in Bulgaria. Although there is no genetic evidence of gray wolf-jackal hybridization in the Caucasus Mountains, there have been cases where otherwise genetically pure golden jackals have displayed remarkably gray wolf-like phenotypes, to the point of being mistaken for wolves by trained biologists.

The gray wolf has very dense and fluffy winter fur, with short underfur and long, coarse guard hairs. Most of the underfur and some of the guard hairs are shed in the spring and grow back in the autumn period. The longest hairs occur on the back, particularly on the front quarters and neck. Especially long hairs are on the shoulders, and almost form a crest on the upper part of the neck. The hairs on the cheeks are elongated and form tufts. The ears are covered in short hairs, which strongly project from the fur. Short, elastic and closely adjacent hairs are present on the limbs from the elbows down to the calcaneal tendons. The winter fur is highly resistant to cold; wolves in northern climates can rest comfortably in open areas at −40° by placing their muzzles between the rear legs and covering their faces with their tail. Wolf fur provides better insulation than dog fur, and does not collect ice when warm breath is condensed against it. In warm climates, the fur is coarser and scarcer than in northern wolves. Female wolves tend to have smoother furred limbs than males, and generally develop the smoothest overall coats as they age. Older wolves generally have more white hairs in the tip of the tail, along the nose and on the forehead.

The gray wolf is generally monogamous, with mated pairs usually remaining together for life. Upon the death of one mated wolf, pairs are quickly re-established. Since males often predominate in any given wolf population, unpaired females are a rarity.