Tissue levels of substance P-like immunoreactivity (SPLI) were determined by radioimmunoassay in incubated cat dental pulps with and without previous electrical stimulation of the inferior alveolar nerve (I.A.N.). The ability of the dental pulp to degrade substance P (SP) was also studied. The pulpal SPLI levels in teeth incubated at 37 degrees C for up to 240 min immediately after removal from the jaws did not differ from those in contralateral unincubated teeth. Following I.A.N. stimulation (3-45 min at 10 V, 15 Hz and 5 ms) and subsequent incubation (30 min at 37 degrees C) of the teeth the SPLI levels in ipsilateral pulps were significantly lower (45% reduction) than those in contralateral unstimulated controls. Incubation of homogenized pulp tissue at 37 degrees C with synthetic bovine SP or 125I-Tyr8-SP led to rapid inactivation of SP, whereas similar incubation of whole blood with 125I-Tyr8-SP had little effect. Endogenous SPLI levels were also rapidly reduced (50% reduction within 3 min) in incubated pulp homogenates. Incubation at a lower temperature (22 degrees C) resulted in a somewhat reduced rate of degradation and incubation with boiled homogenates failed to inactivate SP. The results indicate that the pulp contains enzymes capable of destroying SP and that within the nerve terminals SP is stored in such a way that it is protected against degradation. The data obtained also provide further evidence for a nerve evoked release of SP.