Experiments assessed whether long term exposure to 50 Hz pulsed electromagnetic ®elds with a peak magnetic ®eld of 3 mT can alter the dynamics of intracellular calcium in human astrocytoma U-373 MG cells. Pretreatment of cells with 1.2 mM substance P signi®cantly increased the [Ca 2 ] i . The same effect was also observed when [Ca 2 ] i was evaluated in the presence of 20 mM caffeine. After exposure to electromagnetic ®elds the basal [Ca 2 ] i levels increased signi®cantly from 143 AE 46 nM to 278 AE 125 nM. The increase was also evident after caffeine addition, but in cells treated with substance P and substance P caffeine we observed a [Ca 2 ] i decrease after exposure. When we substituted calcium-free medium for normal medium immediately before the [Ca 2 ] i measurements, the [Ca 2 ] i was similar to that measured in the presence of Ca 2 . In this case, after EMFs exposure of cells treated with substance P, the [Ca 2 ] i , measured without and with addition of caffeine, declined from 824 AE 425 to 38 AE 13 nM and from 1369 AE 700 to 11 AE 4 nM, respectively, indicating that electromagnetic ®elds act either on intracellular Ca 2 stores or on the plasma membrane. Moreover the electromagnetic ®elds that affected [Ca 2 ] i did not cause cell proliferation or cell death and the proliferation indexes remained unchanged after exposure.