The strains of HIV-1 that have caused the worldwide pandemic of acquired immunodeficiency syndrome (AIDS) have been designated as group M viruses. A group of HIV-1 viruses that also cause AIDS but that are characterized by extensive genetic divergence from group M strains have been identified recently and classified as group O viruses. Group O viruses or serologic evidence of group O infection have been reported in patients from West and Central Africa (Cameroon, Gabon, Niger, Nigeria, Senegal, and Togo), nationals of these countries living in Europe, and one French national. The antibody response elicited by group O strains is not consistently detected by enzyme immunoassay (EIA) kits commercially available in Europe and the United States. This report describes a patient in Los Angeles County, California, with recently confirmed HIV-1 group O infection in whom HIV infection was not detected consistently by standard HIV serology.