This investigation provides evidence that a 60-Hz electromagnetic field (EMF) at 1 gauss (G) can drive differentiation of cultured hematopoietic progenitor cells. HL-60 cells are known to differentiate from a nonphagocytic suspension culture to an attached fibroblast-like culture with high phagocytic activity in the presence of the tumor-promoting phorbol ester 12-O-tetradecanoylphorbal-13-acetate (TPA). The effect of 60-Hz EMF at 1 G on differentiation is approximately equivalent to treatment of the cells with 250-500 pg/ml TPA. Furthermore, the effect of both EMF and TPA treatment on differentiation is additive at low TPA concentrations. The results strongly suggest similarities between the effects of TPA treatment and EMF exposure and thus provide an approach for tracing the origins of the molecular effects of EMF exposure, as many transduction pathways in the differentiative process are defined.