The possibility of insulin being enzymatically degraded in contact with the nasal mucosa has been studied in vitro. The insulin concentration was followed during 3 h incubation at 37 degrees C with freshly collected human nasal wash, isolated enzymes from pig and rabbit nasal mucosal tissue, leucine aminopeptidase and microsomal aminopeptidase, respectively. The rate of degradation with human nasal wash was found to be less than or equal to 0.02 microgram/min, which indicates that less than 0.5% of an intranasally applied insulin dose may be destroyed by local enzymes during the time of absorption. The observed degradation was not found to be limiting for an intranasal application of insulin.