Lidocaine may be expected to have a greater effect on neonatal neurobehavior than chloroprocaine because of differences in pharmacology. However, recent reports have been contradictory. Therefore, the purpose of this study was to test the hypothesis that the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) score would be lower when lidocaine is used as a local anesthetic than when chloroprocaine is used, and that any effects would be related to cord blood drug levels. Ninety-nine healthy mother/infant pairs were studied. Clinical characteristics, pharmacological data, and BNBAS scores were collected and analyzed using statistical techniques that included stepwise multiple regression and repeated measures analysis of variance. The results showed, that at less than 5 hr of age, the chloroprocaine group performed significantly better on the motor cluster. At 3 days of age, the chloroprocaine group did significantly better on the autonomic cluster. Cord venous concentrations of lidocaine were the only drug variables that correlated with performance on the autonomic items; the higher the concentration, the poorer the BNBAS score. All of the cluster scores showed significant improvement with age except for regulation of state. Furthermore, the route of delivery was significantly related to regulation of state with cesarean babies performing better. Finally, a three-way interaction (test X delivery X drug) was found for the orientation cluster. The data suggest that the difference in performance on the BNBAS associated with lidocaine is very subtle and that other perinatal factors can influence performance on the BNBAS more than the type of local anesthetic used.