Type I diabetes is associated with a low incidence of asthma. Since sensory neuropeptides including substance P, calcitonin gene-related peptide (CGRP) and somatostatin are of significant influence on bronchomotor responses, we tested the hypothesis that a decrease in the release of these neuropeptides resulting from diabetic neuropathy was associated with an attenuated bronchoconstrictive response to field stimulation (FS). FS (100 stimuli at 20 V, 0.1 ms and 20 Hz)-induced changes in isometric tension of isolated main bronchial rings (2 mm) were studied. In a separate set of experiments, the organ fluid of isolated tracheo-bronchial preparations subjected to FS were tested for substance P, CGRP and somatostatin concentrations by means of radioimmunoassay. Preparations were from either normal rats or those pre-treated with 50 mg/kg streptozotocin (STZ) i.v. 8 weeks preceding the experiments. A separate group of STZ-treated animals were supplied with subcutaneous insulin-delivery (4 IU/day) implants between 4-8 weeks. In addition, a subgroup was formed to study the effect of desensitization with capsaicin. The FS-induced atropine-resistant contraction was significantly attenuated by diabetes with abolition of the capsaicin-sensitive relaxation response. Exogenous CGRP and substance P potentiated, whereas somatostatin inhibited (1 nM-10 mM for each) the FS-induced contractions in rings from either normal or diabetic rats. FS released somatostatin, CGRP and substance P from 0.17±0.024, 0.15±0.022, and 1.65±0.093 to 0.58±0.032, 0.74±0.122, and 5.34±0.295 in preparations from normal animals and from 0.19±0.016, 0.11±0.019, and 0.98±0.116 to 0.22±0.076, 0.34±0.099, and 1.84±0.316 fmol/mg wet wt. in preparations from diabetic rats (for normal vs. diabetic post-stimulation values p<0.01 for each). Insulin supplementation restored neuropeptide release in preparations from STZ-treated rats. The results show that the decreased ability of bronchial preparations to contract in response to FS is associated with a decrease in sensory neuropeptide release in streptozotocin-diabetes in rats.