PURPOSE: To evaluate the presence and concentration of cAMP and cGMP in human nasal mucus in normal volunteers, to relate these findings to age and gender, and to compare normal levels with those in patients with taste and smell dysfunction. METHODS: Nasal mucus was collected over one to four days in 66 normal subjects and 203 patients with smell loss (hyposmia). Samples were centrifuged at 20,000 rpm, the supernatant removed and analyzed for cAMP and cGMP by using a 96 plate technique with a specific spectrophotometric colorimetric ELISA assay. RESULTS: Both cAMP and cGMP were present in human nasal mucus with both cAMP and cGMP significantly higher in normal women than in normal men [men vs. women; cAMP, 0.23+/-0.002 vs. 0.34+/-0.05 (P < 0.05); cGMP, 0.28+/-0.03 vs. 0.63+/-0.12 (P < 0.01)]. Both cAMP and cGMP changed with age; both moieties increased in a U shaped, parabolic pattern reaching a peak at age 41-50 with cAMP diminishing thereafter and then increasing to its highest level over age 70. Both cAMP and cGMP were lower in patients with taste and smell dysfunction than in normal subjects [normals vs. patients; cAMP, 0.31+/-0.05 vs. 0.15+/-0.02 (P < 0.01); cGMP, 0.56+/-0.07 vs. 0.025+/-0.02 (P < 0.001)] suggesting a relationship to olfactory pathology. CONCLUSIONS: This is the first definitive study to demonstrate the presence of these cyclic nucleotides in nasal mucus and the first to reveal decreased levels in patients with impaired taste and smell function. Since olfactory receptor sensitivity decreases with age increased nasal mucus cAMP over age 70 may appear incongruous but suggests one role of cAMP in olfactory function may relate to feedback mechanism(s) whereby its increase over age 70 yr reflects a physiological attempt to enhance diminishing lfactory function through growth and development of olfactory receptor activity.