The virulence of several early and serologically indistinguishable strains of the four original isolations of Semliki Forest virus was defined quantitatively through the response of mice, guinea-pigs and rabbits to intraperitoneal, respiratory and intracerebral administration of virus. There was a clear gradient of virulence against a corresponding gradient in the efficiency of the hosts' protective responses. When the responsiveness of the host was critically balanced against the virulence of the invading virus a transitional state developed in which the groups of infected test animals showed a dual response in which some died and some were protected. This may have been due to the presence in some virus samples of subpopulations of extreme virulence and avirulence. Regardless of the ultimate response being death, incapacitation or benign protection, the efficiency of initial invasion and replication of virus was uniformly high for virus strains of extreme virulence or avirulence.