BACKGROUND: Despite the widespread use of vaccines against feline herpesvirus type1 (FHV_1) and feline calicivirus (FCV), clinical signs are still seen in cat population. Objectives: The aim of this study was to determine the prevalence of FHV-1 and FCV in non vaccinated clinically healthy cats and cats with URTD. Methods: Oropharyngeal and conjunctival swabs were taken from 16 cats with clinical signs of URTD and 26 clinically healthy cats. Reverse transcription polymerase chain reaction (RT-PCR) and polymerase chain reaction (PCR) were performed to diagnose FCV and FHV-1 infections. Results: In cats with URTD, the prevalence rate of FCV (100%) was higher than FHV-1(43%) but in clinically normal cats the prevalence rate of both viruses was about 50%. Clinical signs in cats with FCV was more various than FHV. Also, the prevalence of both viruses co-infection was 30% and half of them showed clinical disease. The results indicated higher rate of both viruses infection especially FCV in domestic cats in Tehran in comparison with other regions. Stomatitis was seen in 50% of cats with URTD. In 50% of cats with corneal ulcers, contrary to our expectations, FCV was detected not FHV-1. Conclusions: It seems that new variants of calicivirus are more virulent and are able to damage other tissues like cornea and conjunctiva. FCV tends to produce more clinical signs than FHV. Also, infection with new variants of FCV and FHV-1 in healthy cats and cats with URTD is much higher than other regions of the world. Therefore, a revision of vaccines and vaccination program, especially for FCV has become a matter of necessity just like other countries.