Growth characteristics of 17D yellow fever virus (17D-YF) and conditions for infection were studied in U937, a macrophage-like, Fc receptor-bearing continuous human cell line. Antibody to 17D-YF was obtained by immunization of normal subjects with 17D-YF vaccine. Cells were infected in the presence or absence of immune whole sera or immunoglobulin fractions. Infection of U937 was temperature dependent; the yield of virus was variable but at low temperature viral titers were consistently higher when infection was established in the presence of antibody. Results of infectious center assays indicated that the increased yield of virus was largely or entirely due to an increase in the number of cells producing virus early in the course of infection. Enhancement of viral growth was mediated by IgG but not IgM fractions of immune sera. Trypsinization of U937 resulted in a 90 to 95% reduction of infection in the absence of antibody but in the presence of antibody viral titers were higher in trypsinized than in nontrypsinized cells. Antibody to 17D-YF, contained in the whole IgG fraction of sera, bound to U937 to mediate infection without first being complexed to virus. Preincubation of U937 with IgG1 but not IgG2 myeloma proteins abrogated antibody-mediated infection. This result is compatible with the known affinities of U937 Fc receptors for specific subclasses of IgG and provides evidence for the role of the Fc receptor in antibody-mediated enhancement of viral growth. Persistent infection characterized by a lack of detectable cytopathogenic effect was established in long-term cultures of U937. This pattern of infection might be related to the unique effectiveness of the 17D-YF vaccine.