Inclusion of spores of Bacillus subtilis var. niger in water-soluble crystals increased their resistance to sterilization with dry heat or with a gaseous mixture of methyl bromide and ethylene oxide. Resistance of spores in glycine crystals to dry heat at 125 C was increased five to 24 times compared with unprotected spores. Size of the crystal and degree of resistance appear to be positively correlated. The dry-heat resistance of spores included in sodium chloride crystals was about six times greater than that of unprotected spores. A gaseous mixture of methyl bromide 964 mgliter and ethylene oxide 642 mg liter was ineffective in sterilizing spores enclosed within these water-soluble crystals, as was ethylene oxide alone. However, if the relative humidity was sufficiently high to dissolve the crystals during exposure to the vapor, viable spore counts were drastically reduced or were negative. Crystal surfaces grossly contaminated with dry spores were sterilized by exposure to gaseous ethylene oxide. Sterilization of heat-labile or moisture-labile materials with a critical requirement for sterility, as in drugs or planetary probes, may be complicated by the presence of spores in naturally occurring water-soluble crystals. This phenomenon is similar to the protection afforded spores entrapped in solid plastics.