In morphine-tolerant rats, a reappearance of morphine catalepsy and a disappearance of the turning behavior characteristic of brain-lesioned tolerant animals were observed under the influence of furosemide and spironolactone. The administration of spironolactone together with daily morphine treatment resulted first in an intensification of the morphine symptoms as measured by catalepsy and a retarded appearance of tolerance, typically characterized by a shift from catalepsy to turning movements in animals with single-sided brain lesions. Nontoxic doses of spironolactone raised the sensitivity of morphine-tolerant rats so that previously tolerated morphine doses become lethal.