Ward et al. (Brain Research 424 (1987) 84-88) have reported that reduced size of the corpus callosum (CC) was associated with a lower degree of paw preference in the mouse strain 129/J but not in the strain BALB/cCF. Both strains show individually different degrees of development of the CC but mice completely lacking CC occur rarely. The mouse strain I/LnJ shows complete agenesis of the CC. Thus, we have compared the degree of paw lateralization by means of a food reaching task in two samples of I/LnJ mice (n1 = 81, n2 = 93) with that of two common mouse strains which show a normal CC (C57BL/6JIbm, n = 44; DBA/2JZur, n = 48). The two samples of I/LnJ mice were tested in different laboratories. The first sample of I/LnJ mice had a mean age of 36 weeks. As compared to the control mice, the males but not the females showed a significantly reduced degree of paw preference. Both, callosal and acallosal mice showed a preference for left choices. The replication sample of I/LnJ mice contained only animals between 6 and 8 weeks old. All of them were ambilateral. There was no side preference and no gender difference. We conclude that congenital absence of the CC is a factor which may substantially interfere with the development of paw lateralization. However, depending on age and gender, about half of the acallosal mice develop a paw preference.