Among the chemical moieties present in human parotid saliva, some, such as gustin or carbonic anhydrase VI, have been useful to distinguish patients with taste and smell dysfunction from normal subjects. To continue these studies we compared levels of salivary cAMP and cGMP in patients with taste and smell dysfunction with those in normal subjects. We were also interested in exploring physiological characteristics of salivary cAMP and cGMP including changes with gender and age because previous studies had not clearly defined these issues. To perform these studies parotid saliva was collected from 61 normal volunteers and 253 patients with taste and smell dysfunction. cAMP and cGMP were measured by a spectrophotometric 96 plate ELISA technique; parotid salivary protein and flow rate were also measured. Both cAMP and cGMP were found in saliva of normal subjects and patients in the detection range of the assay used. In patients mean concentrations of both cAMP and cGMP were lower than in normal subjects; for cAMP levels were lower among both men and women patients. cAMP was 7 to 10 times higher than cGMP in both normal subjects and patients. Concentrations of cAMP were consistently higher in normal women than in normal men. cAMP levels were generally lower and cGMP levels were generally higher than in previously reported studies. There was a complex pattern of change for both cAMP and cGMP with age with concentrations increasing to about age 50, then decreasing, then increasing again at age >70 years.