OBJECTIVE To study the effects of osthole (Ost) on the isolated guinea pig atria and the relationship between Ost effect and Ca2+. METHODS Contractions of left atria were induced by electric stimulations. The contractile amplitude of left atria pre- and post-treated with Ost was measured according to the cumulative concentration method, the drug being added at 15 min intervals, the pA2 or pD2' were calculated. It were measured that the effects of Ost to the positive staircase and to the post-rest potential enhancement. The contractile responses were recorded via an auto-equiolibration recording instrument. RESULTS Ost 10-300 mumol.L-1 and Ver 0.1-30 mumol.L-1 decreased the contractile force and inhibited the isoprenaline-induced restoration of contractile response in the left atria rendered inexcitable by KCl 25 mmol.L-1. Ost and Ver antagonized the CaCl2- and isoprenaline-induced positive inotropic response noncompetively, the pD2' values to Ost were 4.41 +/- 0.13 and 4.90 +/- 0.15, to Ver were 6.53 +/- 0.22 and 6.91 +/- 0.17, respectively. Both of them inhibited the contraction of the left atrium and reversed the frequency-contraction response from positive to negative staircase in the higher dosage (500 and 1 mumol.L-1), but they showed only slight inhibitory effect on post-rest potentiation. CONCLUSIONS Ost was similar to, but much less potent than Ver in inhibiting the isolated guinea pig atria.