BACKGROUND: The luteinising hormone receptor (LHR) is necessary for the stimulation of androgen production and male genital development. It contains three protein polymorphisms: a leucine and glutamine insertion between codons 8 and 9 (LQ+) and two amino acid substitutions (N291S, N312S). OBJECTIVES: To determine whether these LHR polymorphisms are associated with male genital undermasculinisation or the androgen receptor polyglutamine repeat polymorphism (AR(Q)n), which contributes in some cases to the cause of genital undermasculinisation. METHODS: The LHR polymorphisms were assessed by PCR amplification of genomic DNA, followed by restriction enzyme analysis. The frequency of the LHR polymorphisms were compared between an undermasculinised male group (n=75) and a control group (n=55). RESULTS: LQ+ was not independently associated with the undermasculinised group (P=0.09), but it was associated with increased AR(Q)n within the undermasculinised group (P=0.02), particularly for AR(Q)n lengths >or=26 (P=0.002). In the undermasculinised group, homozygosity for N291 (872A/A) was more frequent (P=0.05), whereas homozygosity for N312 (935A/A) was less frequent (P=0.05). The combination of the presence of 872A/A and the absence of 935A/A showed a stronger association with the undermasculinised group than either polymorphism independently (P=0.006). The odds ratio of this genotype compared with any other, between the undermasculinised and control groups was 3.28 (95% confidence interval (CI) 1.33 to 8.08). CONCLUSION: LHR polymorphisms may contribute to genital undermasculinisation.