Inflammation and cardiovascular disease are associated with elevated serum levels of C-Reactive Protein (CRP) and homocysteine. The presence of both molecules in saliva provides an opportunity for development of non-invasive assessments of disease risk. However, salivary CRP and homocysteine reference ranges and their correlation with serum levels are unknown. This study investigated if CRP and homocysteine could be routinely detected in the saliva of healthy adults and the relationship between salivary and blood levels. CRP and homocysteine concentrations were determined using ELISA and enzymatic assays respectively. Homocysteine was detected in only two saliva samples (n = 55). CRP was measurable in all saliva samples (range: 0.05 to 64.3 µg/L; median = 1.2 µg/L) and plasma samples (range: 0.14 to 31.1 mg/L; median = 2.0 mg/L). Regression analysis demonstrated no relation- ship between CRP concentration in saliva and plasma (R2 = 0.001). Generalized linear models including variables such as saliva flow rate and time since eating or drinking also did not pass lack of fit testing. Therefore, a relationship between CRP concentration in saliva and blood could not be established in this group of subjects. More sensitive detection methods are needed to determine if a correlation between salivary and serum homocysteine levels exists.