Crusted scabies is a severe debilitating disease due to hyperinfestation with the ectoparasite Sarcoptes scabiei. Treatment protocols include oral ivermectin and topical scabicides. After single-dose ivermectin, there may be early recrudescence, whereas after 3 doses at 14-day intervals, there is an apparent cure. However, such patients often present again after 6-12 months. To clarify the biology of recurrence, we studied genetic markers in sequential populations of S. scabiei mites from treated patients with multiple episodes of crusted scabies. Individual mites were genotyped at hypervariable microsatellite loci by a fluorescence-based polymerase chain reaction. Results indicated that sequential populations of mites were genetically more similar to each other than to mites from other patients. Although the majority of recurrent scabies is probably due to reinfestation from inadequately treated contacts, there was evidence that in very severe crusted scabies, treatment with even 3 doses of ivermectin 14 days apart may be inadequate and relapse may occur.