Patients with cryptococcal meningitis tend to have recurrences of infection. Although the original strain of Cryptococcus neoformans is assumed to persist in recurrent infections, this assumption has not been tested. Southern blot hybridisation with two genomic DNA probes and pulsed-field electrophoresis of intact chromosomes were used to investigate the genetic relation between initial and relapse isolates of C neoformans from patients with recurrent cryptococcal meningitis. Eleven isolates were obtained from four patients (three with AIDS, one with leukaemia). Isolates from each patient could be distinguished from those of the other patients; however, each patient's initial and recurrence isolates were clonally related. Our results provide strong evidence that clinical recurrences of cryptococcal meningitis result from persistence of the original infecting strain.