To investigate the biochemical effects of pulsed electromagnetic fields (PEMF) on bone in particular and on cell membrane-associated activity in general, we have studied the modification by PEMF of cAMP metabolism in primary calvarial bone cells. We report that PEMF inhibited cAMP accumulation stimulated by bovine PTH(1-34) peptide. After a 1-hr PEMF exposure, the cAMP response to PTH (2-7 min) was decreased in exposed cells to 48-70% (p less than 0.05) of the response of unexposed cells; furthermore, this inhibition disappeared after 10-20 min with PTH. This inhibition occurred at submaximal PTH doses (2.4-7.3 nM) and no effect was observed at maximal PTH doses (24 nM). Thus with PEMF, the dose response curve for PTH became 0.5 log unit less sensitive. PEMF did not affect the cAMP response to cholera toxin and forskolin. However, when submaximal doses of both forskolin (0.5-1.0 microM) and PTH (0.24-2.4 nM) were used, forskolin prevented inhibition of cAMP production by PEMF in the range of fields and stimulus epochs which normally inhibit cAMP production. It is proposed that PEMF inhibits PTH-stimulated coupling of the adenylate cyclase system and that this inhibition does not affect the intrinsic activity of the G-protein and the catalytic subunit.