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Thirty-one documented acquired immune deficiency syndrome (AIDS) cases occurred in Panama during 1984–1987. Twenty-three (74%) patients were homosexual males and all but 2 patients recognized prior to June 1987 have died. To identify risk factors for human immunodeficiency virus infection, 287 male homosexual residents of Panama City were enrolled in a cross-sectional study. Nine had human immunodeficiency virus (HIV) antibody. Travel to the United States, homosexual relations with United States nationals in Panama, and sexual contacts in Panamanian clubs and bars were associated with human immunodeficiency virus infection by logistic regression analysis. Number of different male sex partners per year was identified but did not enter the logistic model at a significant level. To estimate seroprevalence in other high risk populations, 183 Panama City female prostitutes and 55 homosexual males from the rural Azuero peninsula were screened; none were seropositive. Eighty-four percent of Panamanian hemophiliacs had antibody; infection was related to factor VIII transfusions. Two of 182 sickle cell anemia patients and 15 of 7,720 volunteer blood donors were positive.