A polymorphic site of the growth hormone gene (AluI polymorphism) that results in an amino acid change at position 127 of the protein chain (leucine, L to valine, V) has been linked to differences in circulating metabolites and metabolic hormones of calves and bulls and to milk yield traits of lactating cows. Our objective was to investigate the interrelationship of this polymorphism with plasma concentrations of beta-hydroxybutyrate, insulin, IGF-I and leptin in postpartum dairy cows. Blood samples were taken from clinically healthy, spring-calving, group-fed Holstein-Friesian cows (n = 257; 7 large-scale farms) 4-13 days after calving. Of all herds, 100 cows had plasma beta-hydroxybutyrate levels above 1.2 mmol/l and 157 cows were normoketonemic. The proportion of valine carriers and LL cows was not different within groups of normo- and hyperketonemic animals. Genotype was not associated with plasma beta-hydroxybutyrate, insulin, IGF-I and leptin levels either in all of the herds or in the two with the highest proportion of the valine allele carriers (n = 28, 72%). We found significantly lower insulin, IGF-I and leptin concentrations in the presence of hyperketonemia compared to normoketonemic cows. There were strong negative correlations between BHB and the other blood parameters. while insulin, IGF-I and leptin were positively related to each other. In conclusion, in the first two weeks after calving we could not demonstrate any effect of AluI polymorphism on plasma concentrations of beta-hydroxybutyrate and metabolic hormones studied. Hyperketonemia was associated with a significant decrease in insulin, IGF-I and leptin blood levels. We infer that cows homozygous for the leucine allele or carrying the valine allele may have a similar endocrine and metabolic response to the challenge of increased nutrient demand early postpartum and that the presence of hyperketonemia is mainly linked to the hormonal and metabolic changes occurring at the onset of lactation. (C) 2008 Elsevier B.V. All rights reserved.