Capsaicin (1 microM) produces a tetrodotoxin-resistant contraction of the rat isolated urinary bladder ascribable to neuropeptide release from sensory nerves. A second application of capsaicin (1-10 microM) up to 5 h from the first one was ineffective, indicating complete desensitization. However, if the first exposure to capsaicin was made after a prolonged incubation in a Ca-free medium containing EDTA (0.1 mM), a second application of capsaicin (1 microM) was still able to induce a contraction, thus indicating protection from desensitization.