Acallosal and callosotomized subjects usually show impairments on tasks requiring bilateral interdependent motor control. However, few studies have assessed the ability of these subjects to learn a skill that requires the simultaneous contribution of each hemisphere in its acquisition. The present study examined whether acallosal and callosotomized subjects could learn a visuomotor skill that involved a motor control from either both or a single hemisphere. Eleven adult patients, six acallosal and five callosotomized, participated in this study. Seven of these patients had epileptic foci located in the frontal and/or temporal areas and one of the acallosal patients showed bilateral prefrontal atrophy following surgical removal of an orbitofrontal cyst. The performance of the experimental subjects was compared with that of 11 matched control subjects, on a modified version of a serial reaction time task developed by Nissen and Bullemer (Cogn Psychol 1987; 19: 1-32). This skill acquisition task involved bimanual or unimanual key-pressing responses to a sequence of 10 visual stimuli that was repeated 160 times. A declarative memory task was then performed to assess explicit knowledge of the sequence. None of the experimental subjects learned the task in the bimanual condition. Patients with frontal epileptic foci or orbitofrontal damage also failed to learn the task in the unimanual condition when they were using the hand contralateral to the damaged hemisphere. All other subjects, including the acallosal and callosotomized patients with temporal foci, learned the visuomotor skill as well as their controls in the unimanual condition. In spite of the absence of transfer and interhemispheric integration of procedural learning, some of the acallosal and callosotomized patients were able to learn the sequence explicitly. These findings indicate that the corpus callosum and the frontal cortical areas are important for procedural learning of a visuomotor skill. They also confirm the dissociation described by Squire (Science 1986; 232: 1612-9 and J Cogn Neurosci 1992; 4: 232-43) between the declarative and procedural memory systems and extend this dissociation to processes involving simultaneous bihemispheric co-operation.