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In early 2015, the Indiana State Department of Health received a report of 11 confirmed HIV cases occurring among injection-drug users in a rural county in southeastern Indiana, an area where fewer than 5 cases had been reported per year in the past. The new cases were linked to needle sharing and injection of the prescription opioid oxymorphone. As of April 21, HIV infection had been diagnosed in 135 people in this community of 4200 (about 3 per 100 population), with hepatitis C virus coinfection identified in 84% of them. The patients (55% of whom were male) had a mean age of 35; they reported 4 to 15 injections per day with 1 to 6 injection partners each time.