In vivo administration of chloroquine to rats caused an increase in the pH of hepatocyte lysosomes within 1 hr after administration with a return to baseline pH values by 3 hr; continued administration of chloroquine for up to 12 days was unaccompanied by any further changes in hepatocyte lysosomal pH. We interpret these data as evidence against a major role for an increase in the pH of hepatocyte lysosomes in CAC-induced phospholipidosis.