Background: Recent studies have focused on the relationship between human herp esvirus 6 (HHV 6) and multiple sclerosis (MS). Objective: To analyze HHV 6 mes senger RNA expression in patients with relapsing remitting (RR) MS vs healthy b lood donors (HBDs). Design: One hunred fiftyfour subjects were enrolled in the study: 105 patients with [Dr. R. Alvar ez Lafuente, Lab. de Invest. 7a Norte, Hospi RRMS (32 in relapse) and 49 HBDs. Total DNA and messenger RNA were extracted from serum and blood samples, respec tively, and analyzed by quantitative real time reverse transcription polymeras e chain reaction for the detection of 3 HHV 6 immediate early genes (U16/U17, U89/U90, and U94) and both HHV 6 variants (HHV 6A and HHV 6B). Results: Activ e HHV 6 infection was detected in 16%of patients with RRMS vs 0%of HBDs (P=.0 03). Seven patients with RRMS with exacerbation had HHV 6 active replication, a nd the virus remained latent in only 1 of them. We did not find any statisticall y significant difference between HHV 6 active or latent infection for patients in remission (P = .12). Among patients with RRMS with HHV 6 active replication, viral load was higher when they experienced an acute attack than when in remiss ion (P = .04). In those patients with RRMS who had an active infection only, HHV 6A was found. Cell free HHV 6 DNA detected in serum samples confirmed the re sults. Conclusions: The results show that a subset of patients with RRMS experie nce HHV 6 active infection, and there likely is an association between the vira l active replication and relapses; therefore, HHV 6 active infection may imply a greater risk of exacerbations in a subgroup of patients with RRMS. Background: Recent studies have focused on the relationship between human herp virus 6 (HHV 6) and multiple sclerosis (MS). Objective: To analyze HHV 6 mes senger RNA expression in patients with relapsing remitting (RR) MS vs healthy b lood donors HBDs). Design: One hunred fiftyfour subjects were enrolled in the study: 105 patients with [Dr. R. Alvar ez Lafuente, Lab. De Invest. 7a Norte, Hospi RRMS (32 in relapse) and 49 HBDs. RNA were extracted from serum and blood samples, respec tively, and analyzed by quantitative real time reverse transcription polymerase chain reaction for the detection of 3 HHV 6 immediate early genes (U16 / U17, U89 / U90, and U94) and both HHV6 Seven patients with RRMS with exacerbation had HHV 6 active replication, (HHV 6A and HHV 6B). Results: Activation of HHV 6 infection was detected in 16% of patients with RRMS vs 0% of HBDs (P = .0 03) a nd the virus remained latent in only 1 of them. We did not find any statisticall y significa nt difference between HHV 6 active or latent infection for patients in remission (P = .12). Among patients with RRH with HHV 6 active replication, viral load was higher when they experienced an acute attack than when in remission (P = .04 ) In those patients with RRMS who had an active infection only, HHV 6A was found. Cell free HHV 6 DNA detected in serum samples confirmed the re sults. Conclusions: The results show that a subset of patients with RRMS experie nce HHV 6 active infection, and there likely will an association between the vira l active replication and relapses; therefore, HHV 6 active infection may imply a greater risk of exacerbations in a subgroup of patients with RRMS.