In its common modern meaning, a mule is the offspring of a male donkey and a female horse, which is classified as a kind of F1 hybrid. The reverse, the offspring of a male horse and a female donkey, is called a hinny. The term "mule" (Latin mulus) was formerly applied to the offspring of any two creatures of different species – in modern usage, a "hybrid".
The mule, easier to breed and usually larger in size than a hinny, has monopolized the attention of breeders. The chromosome match-up more often occurs when the jack (male donkey) is the sire and the mare (female horse) is the dam. Sometimes people let a stallion (male horse) run with a jenny (female donkey) for as long as six years before getting her pregnant. Mules and hinnies are almost always sterile (see fertile mules below for rare cases). The sterility is attributed to the differing number of chromosomes of the two species: donkeys have 62 chromosomes, whereas horses have 64. Their offspring thus have 63 chromosomes which cannot evenly divide.
A female mule, called a "molly", that has estrus cycles and can carry a fetus, can occasionally occur naturally as well as through embryo transfer. The difficulty is in getting the molly pregnant in the first place.