Since April 21, 2009, CDC has reported cases of respiratory infection with a swine-origin influenza A (H1N1) virus (S-OIV) that is being spread via human-to-human transmission. As of April 28, the total number of confirmed S-OIV cases in the United States was 64; these cases occurred in California (10 cases), Kansas (two), New York (45), Ohio (one), and Texas (six). The viruses contain a unique combination of gene segments that had not been reported previously among swine or human influenza viruses in the United States or elsewhere. Viruses from 13 (20%) of 64 patients have been tested for resistance to antiviral medications. To date, all tested viruses are resistant to amantadine and rimantadine but are susceptible to oseltamivir and zanamivir. The purpose of this report is to provide detailed information on the drug susceptibility of the newly detected S-OIVs, which will aid in making recommendations for treatment and prophylaxis for swine influenza A (H1N1) infection. These data also will contribute to antiviral-resistance monitoring and diagnostic test development.