The influence of interferential current (IFC) on the release of four cytokines was investigated. IFC is an amplitude-modulated 4 kHz current used in therapeutic applications. Human promyelocytes (HL-60) were differentiated to monocytes/macrophages by treatment with calcitriol. Release of tumor necrosis factor a (TNFa) and interleukines 1b, 6, and 8 (IL-1b, IL-6, and IL-8) into the supernatant was measured after exposure to IFC at different modulation frequencies. TNFa release was stimulated about twofold by 4 kHz sine waves alone. The influences of exposure time (5ยฑ 30 min) and current density (2.5ยฑ2500 mA/cm 2 ) were tested. A maximum field effect was found at an exposure time of 15 min and a current density of 250 mA/cm 2 . With these exposure conditions (15 min and 250 mA/cm 2 ), cells were treated at different modulation frequencies and reacted for TNFa, IL-1b, and IL-8 release in a complex manner. Within the frequencies studied (0ยฑ125 Hz), we found stimulation as well as depression of the release. In a second run the cells were activated by pretreatment with 10 mg/ml lipopolysaccharide (LPS) and exposed in the same way as the nonactivated cells. Again the modulation frequency influenced, in a complex way, the induction of TNFa, IL-1b, and IL-8, resulting in a pattern of stimulation and depression of release different from that found in nonactivated cells. For IL-6 production no significant changes were detected in activated or non-activated cells.