Detrusor instability (DI) and detrusor-external sphincter dyssynergia lead to poor bladder emptying and high bladder pressure. Recent results indicate that nitric oxide (NO) is an important transmitter or messenger molecule in autonomic neurotransmission. Adrenomedullin (AM) is a potent vasodilator and natriuretic peptide, originally purified from human pheochromocytoma. Since NO and AM have vasodilatory effects on smooth muscles, we considered them to be of interest in children with DI. We determined the tissue levels of NO and AM in 14 children with DI, and compared these with 6 children with normal bladder activity. Bladder biopsy total nitrite levels (nmol/g tissue) were decreased in children with DI (10.69 +/- 0.91 vs. 12.83 +/- 0.98, P < 0.01). However, AM levels (pmol/g tissue) were increased in the same patients (48.84 +/- 3.52 vs. 28.79 +/- 1.53, P < 0.001). According to our results, decreased NO production probably has a role in the pathophysiology of DI, although increased AM appears to be compensatory. NO may provide a therapeutic target in clinical situations related to DI. However, the functional significance of AM and NO in bladder smooth muscle remains to be determined by further detailed studies.