Although lidocaine HCl is often given to critically ill patients with ventricular tachyarrhythmias, it use is not without hazard. To investigate whether acid-base disturbances and their subsequent effects on molecular ioization influence cardiovascular (CV) response to lidocaine, dogs in normal acid-base balance, metabolic acidosis, respiratory acidosis, and respiratory alkalosis were given 2 or 4 mg/kg lidocaine IV. Heart rate (HR), PR and QT intervals, MAP, LVEDP, LV dp/dt, and LV dp/dt divided by CPIP were measured at intervals. In all groups a slight increase in mean HR occurred after 2 mg/kg. Generally, myocardial contractile force was depressed in direct proportion to dose. Essentially, the CV response to lidocaine was not altered by any clinically remarkable degree by pH disturbances. Responses differing from those observed during normal acid-base conditions could not be significantly correlated with changes in pH or PaCO2. Results suggest that, in the intact animal, the CV effects of lidocaine, administered in therapeutic doses, are not appreciably influenced by clinically encountered states of acid-base imbalance.