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Many pathogens may be responsible of Non Gonococcal Urethritis (NGU) with the possible occurrence of symptomatic and asymptomatic mixed viral and bacterial infections. In particular, genital papillomaviruses (HPVs) have been searched since they are linked to both benign and malignant lesions of the penis and urethra and the presence of a potential male carried state has received limited scrutiny while the screening of sexually active females has received substantial attention.In male patients affected by chronic NGU, the presence of DNA of Chlamydia trachomatis, herpes simplex virus (HSV) type 1 and 2 and human papillomaviruses by PCR and the occurrence of Gram positive and Gram negative micro-organisms, of Mycoplasma hominis and Ureaplasma urealyticum, by conventional cultural methods have been investigated.Results obtained indicated a high percentage of mixed infections, up to 36%. Genital HPV DNA was detected in 31% of specimens positive for two or more agents, and HSV DNA was detected in 10% of studied population.The concomitant presence of different infectious agents could determine latent, sub-clinical or chronic infections with periodic reactivation. In particular results suggest that HPV and HSV may stimulate cytokine production which can up regulate the expression of other infectious agents and may be responsible for latent chlamydial infections characterised by the persistence of this micro-organism in an altered form, viable but in a culture negative state. Therefore an increased awareness of mixed infections is relevant to define the management and treatment of chronic urethritis.