Much of our understanding of the ionoregulatory and excretory physiology of blood-feeding insects can be traced to a series of papers by Simon Maddrell and colleagues in the 1970s and 1980s. These studies of the Malpighian (renal)tubules of Rhodnius prolixus revealed a number of physiological adaptations to the short-term and long-term stresses associated with blood feeding. More recent electrophysiological studies using voltage- and ion-selective microelectrodes have extended our understanding of the mechanisms and control of ion transport by the secretory and reabsorptive segments of the Rhodnius Malpighian tubule. The discovery that the rates of transport of organic anions, urates and Ca2+ are synchronized to coincide with the appearance of the products of blood meal digestion in the haemolymph of Rhodnius has stimulated parallel studies in Drosophila. This recent research has examined how excretory mechanisms for organic cations and organic anions are altered by exposure to such compounds in the diet. These studies also show that the Drosophila Malpighian tubule provides a useful model for analysis of the roles of transporters such as P-glycoproteins and multidrug resistance-associated proteins in the excretion of toxins.