Vaccines against Marek's disease (MD) have historically been prepared from viral strains biologically and, in some cases serologically, distant from the field strains that provide the natural challenge. Although these heterologous vaccines have been effective, it is possible that vaccines prepared from closely related or autologous serotype 1 strains would be advantageous. To test this hypothesis, chickens were vaccinated at hatch with three different serotype I MD vaccine strains, R2/23, 584A/70 and 648A/100, each attenuated by passage in cell culture and determined to provide significant protection against virulent challenge. Vaccinated groups were challenged at day 6 with low passage, fully virulent parent strains (Md11, 584A and 648A). The strains were isolated from different flocks at different times, and represented vv (Md11) and vv+ (584A and 648A) pathotypes. Vaccines were considered to be autologous to the low passage virus of the same strain and heterologous to low passage viruses of other strains. Data from 3 replicate trials showed that all three vaccines provided high levels of protection against each challenge virus. The highest level of protection (mean 82%) was against Md11 challenge and the lowest (69%) level was against 648A challenge. However, no consistent differences were noted in protection by autologous and heterologous vaccines against the same challenge virus. Also, no serological differences were found among the three serotype I strains by indirect immunofluorescence or virus neutralization tests. Thus, autologous vaccination with cell-culture attenuated serotype 1 strains offered no better protection than heterologous vaccination. This suggests that antigenic differences among serotype I vaccines, if any, are less important than other determinants of vaccine efficacy.