This study evaluated the protective ability of cell-free and cell-associated turkey herpesvirus (HVT) vaccine against Marek's disease (MD). Four variables were evaluated: cell-free versus cell-associated HVT; dose of HVT; time of exposure to MD virus (MDV), and comparison of MD challenge virus types. It was determined that gross lesions of MD were more prevalent in chickens placed in an environment at one day of age with three-week-old chickens shedding the CPF-1 isolate of MD, as in chickens given the same doses of the cell-free and cell-associated HVT vaccine but challenged subcutaneously at 2 weeks of age. The results were not significantly influenced by administering larger doses of the HVT vaccine. The CPF-1 isolate of MD was compared with the GA isolate of MD in chickens vaccinated with graded doses of HVT. Challenge with MDV strains was also with graded doses. Both isolates of MD were similar in virulence. However, protection afforded against MD lesions by HVT was significantly lower in chickens challenged with CPF-1 than with the GA isolate.