Zidovudine (AZT) is the main therapeutic agent against HIV vertical transmission and is routinely administered to seropositive pregnant women and their newborns. Toxicity after chronic administration as well as citogenetic effects following developmental AZT exposure has been reported. Furthermore, recent animal data indicate alterations of several behavioral endpoints during the entire lifespan of mice and rats after developmental AZT exposure. In this study, we investigated specific central nervous system (CNS) effects of AZT administration during pregnancy on the offspring. CD-1 mouse females were administered twice daily from day 10 of pregnancy until delivery with either AZT (160 mg/kg) or saline (0.9% NaCl). On PND, 60 male offsprings received an intraperitoneal injection of the D1 receptor agonist 2,3,4,5-tetra-hydro-7,8-diol-1-phenyl-(1H)-3-benzazepine (SKF 38393) (0, 3, and 10 mg/kg), and spontaneous behavior was assessed in an automated activity chamber for 40 min. At variance from what observed in control mice that displayed excessive grooming when administered the higher dose of the D1 agonist, SKF 38393 failed to increase duration of grooming in AZT-treated mice. These data suggest that the D1 receptorial dopaminergic subsystem might be hyporesponsive in mice prenatally exposed to AZT.