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 differenti ated to monocytes/macrophages by treatment with calcitriol. Release of tumor necrosis factor α (TNFα) and interleukines 1β, 6, and 8 (IL‐1β, IL‐6, and IL‐8) into the supernatant was measured after exposure to IFC at different modulation frequencies. TNFα release was stimulated about twofold by 4 kHz sine waves alone. The influences of exposure time (5–30 min) and current density (2.5–2500 μA/c m2) were tested. A maximum field effect was found at an exposure time of 15 min and a current density of 250 μA/cm2. With these exposure conditions (15 min and 250 μA/cm2 ), cells were treated at different modulation frequencies and reacted for TNFα, IL‐1β, and IL‐8 release in a complex manner. Within the frequencies studied (0–125 Hz), we found stimulation as well as depression of the release. In a second run the cells were activated by pretreatment with 10 μg/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 TNFα, IL‐1β, 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. Bioelectromagnetics 21:238–244, 2000. © 2000 Wiley‐Liss, Inc.