Phosphodiesterase (PDE) and nitric oxide synthase (NOS), evaluated in male erectile dysfunction, are currently under study for their role in the female counterpart. We aim to assess PDE-5 and NOS II presence, at messenger Ribonucleic Acid (mRNA) level, in vaginal environment of menopausal women, by using molecular biology techniques.Specimens of vaginal tissue were obtained from 16 menopausal women undergoing surgery for pelvic organ prolapse. The two samples obtained for each patient, one under the urethra (called U) and one on the rest of the vaginal wall (called V), were tested for PDE-5 and NOS II by RT-PCR and by a densitometric semiquantitative analysis.Of the V samples, 81.3% expressed PDE-5 and 100% NOS II. PDE-5 and NOS II expression were revealed in 87.5% of U specimens. A significant difference (P < 0.05) between V and U samples was found in the expression of NOS II (V vs. U: 24.14 vs. 7.25) and PDE-5 (V vs. U: 44.32 vs. 68.57).Our results demonstrated the presence of PDE-5 and NOS II mRNA in periurethral and vaginal tissue of menopausal women. The distribution of PDE-5 and NOD II may indicate a physiologic role in the regulatory function of human vagina.