A model baiting system suitable for the delivery of an oral rabies vaccine to free-ranging raccoons (Procyon lotor) was developed and tested on barrier islands in South Carolina (USA). Features of barrier island physiography and ecology were studied relative to selective bait deployment and site biosecurity. Capture-mark-recapture data were obtained from 228 raccoons. Raccoon density estimates, using a modified census assessment technique, were one raccoon per 1.8 to 2.7 ha. Mean (±SE) and range home area estimates of radio-collared raccoons were 84 (±15.6) ha (27 to 176 ha) by a minimum convex polygon method and 138 (±22.8) ha (43 to 241 ha), by a harmonic mean transformation method. Habitat utilization determinations of radio-collared raccoons were conducted to identify study areas to potentially maximize selectivity of bait towards raccoons and to reduce the absolute number of baits deployed. Island raccoons showed a habitat preference for maritime forest, maritime shrub and marsh areas. Additionally, there was no evidence of inter-island or mainland exchange of ear-tagged or radio-collared raccoons. A disease and mortality survey was conducted to identify baseline pathology and incidental lesions in the target raccoon population, prior to actual vaccination initiation. Thirty-eight percent of 30 clinically suspect raccoons sampled had intracytoplasmic eosinophilic inclusions diagnostic of canine distemper; no other lesions suggestive of viral etiologies were found. Serological surveys for raccoon poxvirus and rabies virus antibodies were negative. Antibody titers to canine adenovirus 1 and 2 indicated a moderate level of exposure (approximately 10 to 16%) in the raccoon population. Overall, 93 to 100% of placebo baits were consistently disturbed by 7 days post-bait deployment, and bait acceptance rates by raccoons ranged from 49 to 85%, by using a modular systems approach to select the optimum combination of bait attractant, biomarker, matrix, density, and distribution. These results suggest that a large proportion (up to 85%) of a free-ranging island raccoon population can be selectively and safely targeted, marked and monitored utilizing a proposed oral bait delivery system for recombinant or other rabies vaccines.