Haldane's rule in evolutionary theory and speciation is:

When in the F1 offspring of two different animal races one sex is absent, rare, or sterile, that sex is the heterozygous (heterogametic) sex.

It was originally formulated by J. B. S. Haldane; since it appears to be usually but not universally true, it is described as a rule rather than a law. (Haldane's Law is "Now my own suspicion is that the Universe is not only queerer than we suppose, but queerer than we CAN suppose.")

In humans, males are the heterozygous sex with XY sex chromosomes, while females are homozygous with XX chromosomes, but in some other animals and plants, the reverse is true. Haldane's rule has a correspondence with the observation that some negative recessive genes are sex-linked and express themselves more often in men than women, such as color blindness or hemophilia.

One possible rationalisation of the rule is that in two subspecies, a gene necessary for fertility or viability be absent from the homozygous chromosome of one of the subspecies, and so not be transmitted to some hybrids with the heterozygous sex. As speciation progresses, this is likely to start with a reduction in fertility, and then of viability, of one of the sexes of hybrids, at which point the rule can be seen; if it then affects both sexes then the two subspecies stop being able to interbreed and become different species.