The plasma concentrations of lidocaine and its two major active metabolites, monoethylglycylxylidide (MEGX) and glycylxylidide (GX), were measured in simultaneously mixed saliva and plasma samples from 16 patients who had received the drug intravenously for at least 12 h. The concentrations of each compound in saliva tended to be greater than those in the corresponding plasma sample, so that the mean saliva-to-plasma ratio for lidocaine was 2.9 (median, 2.65); for GX, 4.7 (median 2.2); and for MEGX, 7.0 (median, 6.4). There was a statistically significant, although rather weak, relationship between the saliva and the total plasma lidocaine concentrations (r = 0.700; n = 16; p less than 0.01) and between the saliva and the free (unbound) plasma lidocaine concentrations (r = 0.509; n = 16; p less than 0.05). When the latter was corrected for the effect of pH, the relationship was significant but still weak (Spearman's P = 0.619; p less than 0.05). It appears that mixed salivary lidocaine concentrations are a relatively poor guide to free drug concentrations at steady state, even if correction is made for pH changes. Other rapid and convenient methods of estimating free plasma lidocaine concentrations are clearly needed.