Mice immunized by single pyrimethamine terminated infections of Plasmodium berghei berghei, strain NK65 or the Nigerian P. berghei-like parasite, N67, were immune to challenge by P.b. berghei, P.b. yoelii strain 17X, P.b. killicki strain 194ZZ and N67. Mice similarly immunized against P.b. yoelii were only immune or N67 resulted in infections comparable to those found in normal mice. Mice immunized against P.b. killicki were similar except that they also possessed some protection against challenge by N67. Evidence was obtained which indicated that the difference between P.b. yoelii and N67 was not associated with the virulence of the parasites. Prolonged exposure to P.b. yoelii infection slightly increased homologous and heterologous immunity. Two lines of parasites were crossed; one of these was derived from P.b. yoelii and the other from N67. They differed in pyrimethamine sensitivity, glucose phosphate isomerase type and the ability to survive in mice immunized against P.b. yoelii. Ten lines of parasites showing the P.b. yoelii characters of pyrimethamine resistance and GPI-1 were isolated in drug treated mice immune to P.b. yoelii challenge. Twenty-one clones were isolated without drug or antibody selection from the parasites resulting from the cross between P.b. yoelii and N67. Sixteen of these clones were classified according to the markers which they possessed and six were found to be recombinant in character. The experiments showed that genetic recombination occurred as a frequent event in P. berghei and involved factors which control the cross-immunity produced following infection with these parasites.