Background and Objectives: Acute upper respiratory tract infections are the most frequent acute illnesses worldwide.This study has been undertaken for determining the diagnostic importance of Human Rhinovirus and other associated DNA/RNA viruses including human Respiratory Syncytial virus; Human Metapneumovirus; Human parainfluenza virus 1-4; human coronavirus; Human B, C, and E Adenovirus; and Human Bocavirus in common cold disease.Further, to detect the role of some immunological parameters including complement three and rhinovirus Ag (RhV-Ag) in rhinovirus infection.Patients and methods:The samples of 84 individuals infected with common cold were collected and studied.Viral nucleic acids either DNA or RNA were extracted and amplified using real-time multiplex PCR.Results: The most common type causative agent was hRv which accounted for 56.1% followed by hRv+hRSV-hMpv, 12.19% and hRv+hAdv-hBov, 9.75% respectively.Also, the most rarely infection was hRSV-hMpv which found only in one case.On the other hand, complement three was used as a potent immuno-parameter to detect the level in a sample of 80 tested individuals infected with human rhinovirus at which it was found that there is a simple linear correlation coefficient matrix of the variables C3 and RhV-Ag.Conclusion: The study suggested that multiplex RT-PCR is a rapid, cost-effective, specific and highly sensitive method for detection of respiratory viruses including rhinovirus.Further, this study has focused a highlight on the critical roles of C3 in the pathogenesis of rhinovirus infection.Furthermore, RhV-Ag was found to be significantly correlated with the complement C3 at p<0.05 and RhV-Ag cannot be predicted using complement C3. INTRODUCTION:Human rhinoviruses (HRVs) are responsible for more than one-half of cold-like illnesses and cost billions of dollars annually in medical visits and missed days of work.HRVs are traditionally associated with upper respiratory tract infection, otitis media, and sinusitis.