1. The inhibitory action of lorcainide on the myocardial Na(+)-K(+)-ATPase (EC 3.6.1.3) activity was studied in guinea-pig heart preparations at medium K+ concentrations of 2.5, 5.0 and 10 mM. 2. Lorcainide exhibited characteristically similar concentration-dependent inhibitory effects at all three K+ concentrations tested. However, the inhibitory potencies were significantly increased at decreased K+ concentrations. 3. The IC50 values were 10.4 +/- 3.2 microM at 2.5 mM, 28.3 +/- 7.9 microM at 5.0 mM and 40.7 +/- 9.2 microM at 10.0 mM K+ respectively. Thus, reduction in the K+ concentration from the 'standard' 5.0 to 2.5 mM enhanced the inhibitory potency of lorcainide, the effective concentrations being shifted towards much lower ranges, while increasing it to 10 mM on the other hand produced opposite but less marked effects. 4. These results show that the inhibition of myocardial Na(+)-K(+)-ATPase activity by lorcainide depends on the K+ concentration of the incubation medium. These effects are probably related to the mechanism by which lorcainide interferes with the electrogenic Na+/K+ pump activity of the enzyme, and hence may contribute to some of its cardiac actions.