We use Wright’s distribution of equilibrium allele frequency to demonstrate that hybrids between populations interconnected by low to moderate levels of migration can have large positive heterosis, especially if the populations are small in size. Beneficial alleles neither fix in all populations nor equilibrate at the same frequency. Instead, populations reach a mutation–selection–drift–migration balance with sufficient among-population variance that some partially recessive, deleterious mutations can be masked upon crossbreeding. This heterosis is greatest with intermediate mutation rates, intermediate selection coefficients, low migration rates and recessive alleles. Hybrid vigour should not be taken as evidence for the complete isolation of populations. Moreover, we show that heterosis in crosses between populations has a different genetic basis than inbreeding depression within populations and is much more likely to result from alleles of intermediate effect.