In April 2008, a clinical reference laboratory in New Mexico notified the New Mexico Department of Health (NMDOH) of a cluster of unexplained agranulocytosis cases confirmed by bone marrow histopathology during the preceding 2 months. NMDOH began an investigation, which identified cocaine use as a common exposure in 11 cases of otherwise unexplained agranulocytosis during April 2008-November 2009. In the midst of the NMDOH investigation, in November 2008, public health officials in British Columbia and Alberta, Canada, reported detecting levamisole (an antihelminthic drug used mainly in veterinary medicine and a known cause of agranulocytosis) from clinical specimens and drug paraphernalia of cocaine users with agranulocytosis. In January 2009, NMDOH posted a notification of its findings on CDC's Epidemic Information Exchange (Epi-X) and notified poison control centers. In a separate investigation during April--November 2009, public health officials in Seattle, Washington, identified 10 cases of agranulocytosis among persons with a history of cocaine use. Of the 21 cases, levamisole was detected from clinical specimens in four of the five patients tested. According to the Drug Enforcement Administration (DEA), as of July 2009, 69% of seized cocaine lots coming into the United States contained levamisole as an added agent. This report summarizes the investigations in New Mexico and Washington, which suggested that levamisole in cocaine was the likely cause of the agranulocytosis. Health-care providers should consider these findings in the differential diagnosis of agranulocytosis, and public health officials should be aware of cases of agranulocytosis associated with cocaine use.