The effects of administration of capsaicin to developing and adult Sprague-Dawley rats on substance P-containing primary afferent and peripheral adrenergic nerves were analysed by histochemical and neurochemical techniques. In control rats a relatively dense innervation with substance P-immunoreactive fibers was seen in the iris, while 10 weeks after a single neonatal injection of capsaicin (50 mg/kg s.c.) a moderate loss of substance P-immunoreactive nerve fibers was observed. The substance P level was decreased by 60%, while the noradrenaline level, 3H-noradrenaline uptake in vitro and the noradrenaline nerve density were unaltered. Repeated injections of capsaicin (2 x 50 mg/kg, 3 x 20 mg/kg s.c.) for 5 weeks to developing rats led to a very marked decrease of the substance P level and an almost complete disappearance of substance P-immunoreactive fibers in the iris, when analysed at 10 weeks of age. The noradrenaline level in the iris was significantly increased (+42%), while no significant changes in noradrenaline level were observed in heart auricula or superior cervical ganglion. The uptake in vitro of 3H-noradrenaline in irides and heart auriculae, as well as the noradrenaline terminal density in the dilator plate and surrounding blood vessels in the iris, were unaffected by repeated capsaicin treatment to developing rats. Capsaicin administration to adult rats (50 mg/kg s.c.), leading to a profound decrease in substance P, did not affect the noradrenaline levels at 24 hr after the injections. The results indicate that an extensive sensory denervation with capsaicin during development can induce an increase of noradrenaline levels in sympathetic nerve terminals in a target area (rat iris) with a rich SP-ergic sensory innervation, although the sympathetic terminal density is not influenced. Furthermore the increase in noradrenaline seems to require an extensive loss of SP-immunoreactive fibers and not solely a reduction of SP levels.