<i>Background/Aims:</i><i>TAC3 </i>and <i>TACR3</i> have recently been shown to be causative genes for an autosomal recessive form of isolated hypogonadotropic hypogonadism (IHH). Here, we report a Japanese female with IHH and compound heterozygous <i>TACR3 </i>mutations and her heterozygous parents, and discuss the primary lesion for IHH and clinical findings. <i>Case Report:</i> This female was identified through mutation analysis of <i>TAC3</i> and<i> TACR3</i> in 57 patients with IHH. At 24 years of age, an initial standard GnRH test showed poor gonadotropin response (LH <0.2–0.6 IU/l), whereas the second GnRH test performed after GnRH priming (100 µg i.m. for 5 consecutive days) revealed ameliorated gonadotropin responses (LH 0.3–6.4 IU/l; FSH 2.2–9.6 IU/l). The mother exhibited several features suggestive of mild IHH, whereas the father showed an apparently normal phenotype. <i>Results:</i> She had a paternally derived nonsense mutation at exon 1 (Y145X) and a maternally inherited single nucleotide (G) deletion from the conserved ‘GT’ splice donor site of intron 1 (IVS1+1delG). <i>Conclusions:</i> The results suggest hypothalamic dysfunction as the primary cause for IHH in patients with biallelic <i>TACR3</i> mutations and clinical manifestation in heterozygous females, together with the rarity of <i>TAC3</i> and <i>TACR3</i> mutations in patients with IHH.