Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) levels may reflect changes in central noradrenergic and dopaminergic activity, respectively. The relationship between MHPG and HVA in saliva and plasma was investigated to evaluate the utility of salivary metabolite measurement as a relatively noninvasive and useful alternative to plasma analysis. MHPG and HVA in saliva and plasma, collected concurrently, from 12 healthy volunteers, were measured by high-performance liquid chromatography. Concentration of free MHPG in saliva correlated significantly with plasma free MHPG. Salivary free MHPG was significantly higher than in plasma. Enzymatic hydrolysis of conjugated MHPG corroborated other work that plasma free MHPG, MHPG-glucuronide, and MHPG-sulfate were in roughly equal proportions. Unpredictably, in saliva, free MHPG was greater than 80% of the total. Salivary and plasma free HVA concentrations also correlated significantly, but salivary HVA levels were significantly lower than in plasma. Conjugated HVA was consistently less than 10% of total both in saliva and plasma. These findings suggest that salivary MHPG and HVA can reflect plasma metabolite levels. Although local factors may influence their formation and concentration in saliva, large changes in plasma free MHPG or HVA could be reflected by parallel changes in saliva.