Random amplified polymorphic DNA (RAPD) was optimized and used to distinguish between the varieties and serotypes of Cryptococcus neoformans. The RAPD technique distinguished between serotypes A, D or AD within C. neoformans var. neoformans, and revealed further differentiation within each serotype. Four RAPD profiles were clearly recognizable within C. neoformans var. gattii, although its two serotypes, B and C, were only differentiated with one primer combination out of seven.