Objective. L-type Ca²⁺ channel (CC) blockers (CCBs) reduce blood pressure more effectively in hypertensive than in normotensive subjects. Several attempts have been made to explain this unique feature. The depolarization of the resting potential by hypertension not only favours the inactivated state of the CC, but also increases window L-type Ca²⁺ influx via open, non-inactivated CC. Methods. The present study investigated whether the CC agonist BAY K8644 and whether nifedipine, verapamil or diltiazem, representatives of different CCB classes, alone or in combination, modulated window Ca²⁺ influx (Fura-2 method) and isometric contraction during depolarisation of C57Bl6 mouse aorta segments with 50 mM K⁺. Results. High K⁺-induced contractions were biphasic. The fast force component coincided with Ca²⁺ influx via a population of CC that exhibited fast activation and then inactivation. This component was significantly less sensitive to CCBs than the slow, sustained force component, which was attributed to voltage-dependent, but time-independent Ca²⁺ influx displaying incomplete inactivation (window). BAY K8644 (30 nM) shifted the contraction window to lower extracellular K⁺ concentrations and decreased the efficacy of CCBs to inhibit isometric contractions. On the other hand, conditions that favoured window Ca²⁺ influx increased their inhibitory efficacy. Conclusion. Results suggest that inhibition of window L-type Ca²⁺ influx may play a dominant role in the anti-hypertensive effects of CCBs.