The growth characteristics of the human syncytium-forming virus (HSFV) were examined in several human cell lines of normal and malignant origins and composing of either fibroblastic or epithelial-like cells. Virus production occurred only in the fibroblastic diploid cell lines: HEF (human embryonic cells, Flow #5,000) and HFDL #645 (human fetal diploid lung), but not in the epithelial-like heteroploid cell lines: RA (a continuous line of human amnion), #999 (human bone marrow), and KB (carcinoma of the nasopharynx). While the single-cycle growth pattern of the virus in HEF and HFDL #645 cell lines were essentially similar, the virus yield per cell was greater in the HFDL #645 cells. Furthermore, the physiological state of the cell had a marked effect on virus production. Subconfluent actively growing HFDL #645 cells produced higher yields of virus than density-inhibited confluent HFDL #645 cell cultures. The replication of HSFV was inhibited by actinomycin D at concentrations that did not interfere with poliovirus replication (0.001 to 0.01 microgram/ml). Pretreatment and posttreatments of infected cell cultures with either the polycation polybrene (hexadimethrine bromide) or the synthetic glucocorticosteroid dexamethasone did not enhance HSFV production.