The haploid myxamoebae of Physarum polycephalum reversibly differentiate to form dormant microcysts under conditions of starvation. The thin-walled cysts can be selective recovered from a cell suspension which has been treated with the surfactant Triton X-100 to lyse amoeboid forms. Excystment, which is initiated by suspension in liquid medium, is inhibited by antibiotics which block protein synthesis. Cysts of drug resistant mutants excyst rapidly in media containing sufficient antibiotic to maintain drug sensitive strains in the encysted state. The selective survival of non-excysted cells following Triton X-100 treatment has been employed to enrich for drug sensitive mutants. Several anisomycin sensitive mutants have been isolated, one of which has been analysed genetically. The possible applications of this mutant enrichment technique are discussed.