Potassium selective ion channels play an important role in the regulation of vascular tone. Particularly important is the class of K+ (KATP) channels modulated by intracellular ATP, which are normally closed at physiological intracellular ATP concentrations (ATPi) but open when ATPi decreases. KATP channels play an important role in the relaxation of vascular smooth muscle, including that of coronary vessels. Recent data suggest that coronary flow under normal conditions may be tonically controlled by KATP channels. Coronary KATP channels are activated by adenosine released during exercise, hypoxia or ischemia. They also constitute the main site of action of many drugs. Physiologic regulation of these channels is not fully understood. Protein kinase C (PKC) modulates coronary flow, probably via an effect on KATP channels. Implications are that drugs interacting with the KATP channels may change basal coronary flow under normal conditions. The PKC modulation may be important, given its role in mediating the response to neurotransmitters and hormones. In addition, since PKC isoform expression and activity can be modified during disease conditions, the enzyme may be partially responsible for pathologic reduction in coronary flow.