Vaginal delivery of 200mg or 25mg dapivirine from intravaginal rings (IVRs) was evaluated over a 7-day period in two phase 1 safety trials (IPM001 and IPM008, respectively) in a total of 25 healthy women 19 to 46 years of age. The IVR was generally safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Across both studies, dapivirine concentrations in vaginal fluids measured at the introitus, cervix, and ring area were within the mean range of 0.7-7.1μg/ml. Mean dapivirine concentrations in vaginal and cervical tissues on day 7 were 0.3-0.7μg/g in IPM001 and 1.5-3.5μg/g in IPM008. Mean plasma concentrations of dapivirine were <50pg/ml. Dapivirine from both IVRs was successfully distributed throughout the lower genital tract at concentrations >1000× the EC 50 against wild-type HIV-1 (LAI) in MT4 cells suggesting that IVR delivery of microbicides is a viable option meriting further study.