Thirty-seven percent (15/41) of patients with human T-cell lymphotropic virus type III (HTLV-III) disease (acquired immunodeficiency syndrome [AIDS] or AIDS-related complex) sequentially evaluated at Walter Reed Army Medical Center, Washington, DC, acquired this infection from a partner(s) of the opposite sex. Demographic features of these 15 patients (ten males and five females) differed substantially from those for patients reported to the Centers for Disease Control. Heterosexual contact with partners who developed AIDS or who were at risk for AIDS was confirmed in six patients. The remaining nine patients had multiple (greater than 50) heterosexual partners and/or sexual contact with prostitutes. The method of sexual activity did not appear to be related to disease acquisition; however, this study clearly demonstrated that receptive anal intercourse was not a requirement. The observations reported herein provide further epidemiologic evidence to support the occurrence of bidirectional heterosexual transmission (both male to female and female to male) of HTLV-III infection and disease.