Background: Lyme disease is the most prevalent vector-borne disease in the USA with cases continuing to increase. Current control measures have not been shown to be impactful, and therefore alternatives are needed. Treating pathogen reservoirs with low dose systemic acaricides in endemic areas may provide a useful tool for disrupting the cycle of the vector and pathogen. The purpose of this study was to determine the efficacy of a 0.005% fipronil bait, presented orally to white-footed mice, in controlling blacklegged tick larvae (larvae). Methods: Sixty mice were assigned to 3 treatment groups and three untreated control groups. All individually housed mice in treatment groups were exposed to 0.005% fipronil bait for 48 hours. Larvae were manually applied to mice within feeding capsules at one of three timepoints: Day 1, Day 9 and Day 15 post-exposure. For 4-days posttick attachment, replete larvae were collected from water moats underneath each cage and attached larvae were observed by microscopy. Plasma from 4 treated mice at Day-1, Day 13 and Day 19, and 4 control mice (n = 16) was collected to obtain fipronil plasma concentrations (CP). Results: Fipronil bait did not appear to produce neophobia in mice, as the amount of bait eaten at 24-and 48-hours exposure did not differ significantly. The 48-hour fipronil bait exposure prevented 100% of larvae from feeding to repletion at Day 1, Day 9 and Day 15 post-treatment. Within the treatment groups, all larvae observable within the capsules expired and were prevented from detaching by Day 4. In contrast, within the control groups a total of 502 replete larvae were collected from moats and 348 larvae observable within the capsules successfully detached. CP averaged 948.9, 101.2 and 79.4 ng/ml for mice euthanized at Day 1, Day 9 and Day 15, respectively. No fipronil was detected in control mice. Conclusions: We provide early indication that low dose fipronil bait, orally presented to white-footed mice, can effectively control blacklegged tick larvae. Future research should modify the exposure duration and post-exposure tick attachment timepoints to simulate various field scenarios under which successful efficacy might be obtained. Low dose fipronil bait could provide a cost-effective, practical means of controlling blacklegged ticks and other arthropod vectors.