Transforming growth factor-alpha (TGFalpha) is a well-known regulator of many developmental processes, and is expressed heavily in basal forebrain and striatal regions. When TGFalpha is reduced in Waved-1 (Wa-1) mutant mice, brain anatomy, biogenic amines, stress response, and behavior are normal prior to, but altered following puberty. As an initial screen for possible alterations in nigrostriatal and mesolimbic dopamine (DA) systems, we tested adult Wa-1 mutant mice in an open field, following acute injection with cocaine (15 mg/kg). Wa-1 mice exhibited significantly greater ambulatory distance, number of ambulatory episodes, and cocaine-induced motor stereotypies than do controls. These data indicate that adult Wa-1 mice are hypersensitive to the locomotor effects of cocaine and provide a new potential link between neurodevelopmental processes and adult psychostimulant responsiveness.