Pregnancy-related anatomic and physiologic changes result in altered pharmacologic and toxicologic responses to local anesthetics. Reductions in serum protein binding have been implicated in enhanced toxic effects. Previous studies have demonstrated these reductions in protein binding only in the term parturient. The present study defines the pattern of protein binding changes of lidocaine throughout gestation. Venous samples were obtained from pregnant patients of varying gestational age, as well as from nonpregnant control patients. The percent free drug at a fixed concentration (2 μg/mL) was determined for each sample using an ultrafiltration technique. The free concentration of lidocaine increased significantly throughout gestation, reflecting a corresponding decrease in protein binding. However, these changes were small compared to those in the nonparturient, which suggests that toxicity to lidocaine should not vary during pregnancy.