Parotid salivary levels of cyclic adenosine monophosphate (cAMP) have been previously demonstrated to be lower than normal in patients with taste and smell dysfunction. To define these results more fully, we analyzed parotid salivary levels of cAMP and cyclic guanosine monophosphate (cGMP) with respect to severity of smell loss in these patients. Smell loss severity was defined by psychophysical measurements of olfactory function and classified into 4 types from most severe to least severe loss. This resulted in patients exhibiting, in order of loss severity (from greatest to least), anosmia > type I hyposmia > type II hyposmia > type III hyposmia. Parotid saliva cAMP and cGMP were measured independently using a sensitive spectrophotometric 96-plate enzyme-linked immunosorbent assay technique; mean levels were categorized by clinical classification of loss severity. As smell loss severity decreased, salivary cAMP and cGMP levels increased consistently with each stepwise change of clinical loss severity. This is the first demonstration of biochemical changes in saliva associated with a quantitative classification of smell loss. These results reflect a biochemical method to identify and classify patients with smell loss in some respects similar to initial typing of serum lipid levels to assist in risk classification of patients with cardiovascular disease.