Following intracerebral inoculation of 1-day-old chicks, only APMV-1 strain BC, APMV-3, and (to a much lesser extent) APMV-8 could be detected in brain tissue samples. With APMV-1, virus neurotropism depends on the presence of a furin cleavage site, since secretory proteases are unavailable in the brain [37] . The lack of neurotropism of the APMV-1 strain LaSota is consistent with this idea. However, APMV-3 appears to be an exception, since it lacks a furin site and is dependent on added protease in cell culture and thus presumably dependent on secreted protease in vivo, yet it replicated efficiently in the chick brains and neutronal cells in vitro. Interestingly, however, while APMV-3 was clearly neurotropic, it caused no disease or death and thus was not neurovirulent. These findings indicate that the simple paradigm that neurotropism depends on the presence of a furin cleavage site does not hold for APMV-3. Furthermore, it shows that neurotropism by an APMV does not necessarily confer neurovirulence. Our previous study with replacement of the APMV-2 F protein with that of APMV-1 BC suggested an important role for the BC F protein in virus neurotropism, neuroinvasiveness, and neurovirulence in 1-day-old chicks [38] . Based on the generally held model for APMV-1 pathogenesis, it would have been reasonable to suggest that the presence of the furin site in the BC F protein was the major determinant of the observed neurotropism, neuroinvasiveness, and neurovirulence. However, the present study challenges the predominant role for the cleavage site, and suggests that other features of the F protein may be involved in the observed neurotropism, neuroinvasiveness, and neurovirulence. Evaluating the difference in the roles of the F proteins in virus neurotropism versus neurovirulence may provide information on these activities and may help design safer vaccines for neurotropic pathogens.