The spectrum of recessive disease mutations in a population reflects the history of its peoples. We have previously identified mutations on 241 out of 242 investigated Northern Irish phenylketonuria chromosomes (Zschocke et al., Am J Hum Genet 57:1311-17, 1995). Subsequently we undertook to link the common mutations to the different peoples who have contributed to the Irish genepool. I65T is the second commonest PKU mutation in Ireland as well as Spain. It was probably present in the original Palaeolithic peoples of Western Europe who arrived in Ireland in the Mesolithic period, after 8000 BC. R408W (haplotype 1) in contrast, the commonest Irish PKU mutation, may have been prevalent in the Neolithic farmers who settled after 4500 BC. No mutation was identified that could represent European Celtic populations. This supports the view that the adoption of Celtic culture and language in Ireland did not involve major migration from the continent. Several less common mutations can be traced to the Norwegian Atlantic coast and were probably introduced into Ireland by Vikings, either directly or through their descendants immigrating from Scotland. This indicates that PKU has not been introduced to Norway from the British Isles, as has been previously argued. The rarity in N. Ireland of IVS12nt1, the commonest mutation in Denmark and England, indicates that the English colonialisation of Ireland over the centuries did not alter the local genepool in a direction that could be described as Anglo-Saxon. Our results show that culture and language of a population can be independent from their genetic heritage.