Several therapeutic effects including those on digestive and gynaecological disorders, against asthma and dyspnea have been described for the seeds of Nigella sativa. In the present study, the effects of aqueous and macerated extracts from Nigella sativa on heart rate and contractility of the isolated heart were examined. Isolated guinea-pig hearts were perfused through aorta in the Langendorff mode. Heart rate (HR) and contractility were determined on the presence of four concentrations of aqueous and macerated extract from Nigella sativa (0.5, 1.0, 2.0 and 5.0 mg%) and diltiazem, a calcium channel blocker (0.1, 1, 10 and 100 microM) in comparison with baseline values in two different groups of experiments as follows: 1) Perfused heart with ordinary Krebs solution (group 1 experiments, n = 9). 2) Perfused heart with calcium free Krebs solution (group 2 experiments, n = 8). In group 1 three higher concentrations of diltiazem (1, 10 and 100 microM) and both extracts (1.0, 2.0 and 5.0 mg%) showed a significant reduction in heart rate (P < 0.001). However, only two larger concentrations of diltiazem (10 and 100 [microM) and macerated extract (2.0 and 5.0 mg%) and three concentrations of the aqueous extract (1.0, 2.0 and 5.0 mg%) caused a significant reduction in heart contractility in this group (P < 0.001). In group 2 only 100 microM diltiazem, caused significant reduction in heart contractility. However, two concentrations of macerated extract (2.0 and 5.0 mg%) and three higher concentrations of aqueous extract (1.0, 2.0 and 5.0 mg%) caused significant reductions in heart rate and contractility in this group (p < 0.05 to p < 0.001). There were significant negative correlations between concentrations of both extracts and diltiazem and their effect on heart rate and contractility in both groups (p < 0.01 to p < 0.001). These results showed a potent inhibitory effect of both extracts from Nigella sativa on both heart rate and contractility of guinea pig heart that was comparable and even higher than that of diltazem. The results of the present study may be due to calcium channel inhibitory or an opening effect for the plant on potassium channels of the isolated heart.