The exact aetiology of pityriasis rosea (PR) is still unknown as various researches exist aiming to explain the exact cause. The role of Human Herpes Virus(HHV)-6 & HHV-7 DNA in PR patients has been evaluated in many studies with variable results. The rationale behind the use of antiviral in PR is that the course of the disease follows that of a viral exanthem and also probable involvement of HHV 6 and 7 in its etiopathogenesis. The current case-control study aimed at evaluation of the possible relation between HHV-6 & HHV-7 and PR through detection of HHV-6 & HHV-7 DNA in PR patients in comparison to controls and also illumination the therapeutic efficacy of Acyclovir in PR treatment.Based on the number of positive cases for HHV-6 and HHV-7 in the results of the present study on 30 PR patients, we can conclude that HHV-6 and HHV-7 may play a part in the pathogenesis of PR in some patients. Although PR is a self-limited disease which resolves within three weeks to three months, this study revealed that the difference between the treatment groups regarding the course of the disease was statistically significant and oral Acyclovir is helpful in rapid decreasing the severity and shortening the course of the disease in some patients, making those patients satisfied with the rapid cure. This clinical trial, although small, suggest a therapeutic benefit from oral Acyclovir in shortening the course of the disease.