Fifteen Paracoccidioides brasiliensis isolates were discriminated by the RAPD analysis into two groups with only 17% of genomic identity. The ability of P. brasiliensis isolates to invade tissues was studied in an experimental model using susceptible B10.A mice. The analysis was performed according to the severity of the lesions including the number and size of the granuloma, the number and dissemination of fungi to different organs. The isolates from two RAPD groups demonstrated a marked difference in their virulence patterns for B10.A mice. The isolates Pb S, 662, Bt and 166 (group I) elicited localized infection restricted to the liver showing compact epithelioid granuloma with few fungi in the early post-infection period (slightly virulent). On the other hand the isolates Pb 01 and 7455 (group II) elicited a disseminated infection with a mixed suppurative and looser granulomatous inflammation, showing extensive areas of necrosis and large numbers of viable fungal cells (highly virulent). These results are strong evidence for correlation between RAPD patterns and the virulence degree of P. brasiliensis.