Charles Darwin, who was married to his first cousin, Emma Wedgwood, was one of the first experimentalists to demonstrate the adverse effects of inbreeding and to question the consequences of consanguineous mating. He documented the phenomenon of inbreeding depression for numerous plant species, and this caused him to worry about the health of his own children, who were often ill. To determine whether Darwin's fears were justified, we constructed a pedigree of the Darwin/Wedgwood dynasty from the large quantity of genealogical information published on these families. The inbreeding coefficients (F) computed from the pedigree show that Darwin's children were subject to a moderate level of inbreeding (F = 0.0630), and the progeny of related families had still higher inbreeding values (e.g., F = 0.1255 for the progeny of Henry Wedgwood, Emma Wedgwood's brother). The analysis of a sample of 25 Darwin/Wedgwood families belonging to four consecutive generations shows a statistically significant positive association between child mortality (death at or before the age of 10 years) and inbreeding coefficient detected by means of nonparametric tests (τ = 0.309, P = 0.040). Our findings suggest that the high childhood mortality experienced by the Darwin progeny (3 of his 10 children died at age 10 or younger) might be a result of increased homozygosity of deleterious recessive alleles produced by the consanguineous marriages within the Darwin/Wedgwood dynasty.