The protective effect of specific vaccination against Plasmodium berghei (P. berghei) was compared in terms of survival percentage in DBA/2, C3H, outbred albino mice and in two lines of mice produced by selective breeding for either high or low antibody responsiveness to sheep erythrocyte (H and L lines respectively). The efficacy of induced protection varies according to genetic constitution. It is very strong in H line and albino mice, intermediate in DBA/2 and very weak in L line and C3H. The inheritance of post-vaccinal resistance to infection was studied in F1 hybrids and backcrosses between C3H and the other lines. The control was polygenic in all cases. The dominance of the characteristic depends on the strain combination. On the whole the results suggest the non-identity of the genes controlling protection in the various lines. The lack of a quantitative parameter for a more precise genetic analysis of protective immunity in inbred lines is stressed, since both anti-P. berghei antibody production and parasitaemia proved to be unreliable.