The relative virulence of Cryptococcus neoformans serotypes A, B, C and D in four mouse strains was assessed by measuring their migration from the foot-pad of the animals to the spleen, lungs and brain in 6-week-old DBA/2, BALB/c, A/J and a hybrid mouse strain by re-isolating yeasts from the internal organs. Comparable doses of each C. neoformans serotype were inoculated into the foot-pads of the mice. C. neoformans var neoformans strains A68, D52, A-(IN) and D-(IN) were more virulent than C. neoformans var gatti strains B112 and C18. However, the differences in the relative virulence of the var neoformans and the var gatti serotypes for the mouse strains were not significant (p > 0.05). Re-isolation of yeasts from mice showed that the BALB/c mice, in particular, and the DBA/2 mice were more susceptible to disseminated C. neoformans infection. The virulence of C. neoformans serotypes through foot-pad inoculation of mice was established.