The technique of perfusing isolated tubular segments from rabbit kidneys was used to study macula densa (MD) control of renin secretion. Renin secretion was found to be markedly and reversibly increased when perfusate NaCl concentration was reduced. This response of renin secretion occurred within the physiological concentration range, i.e. between 80 and 20 mM. The stimulatory effect of reduced NaCl was seen even when total solute concentration was kept constant. In this preparation a reduction of NaCl concentration was a stronger stimulus than a fall in NaCl load. Loop diuretics were found to stimulate renin secretion. Suppression of renin secretion was seen when most of the Na was replaced by Rb or choline, but not when Cl was replaced with isethionate or acetate. Activation of adenosine-1-receptors inhibited MD-stimulated renin secretion, an effect that was blocked by an A1-antagonist. This agent partially blocked NaCl-induced inhibition of renin release, suggesting a possible role of adenosine in MD control of renin secretion.