Although talc has been used as a pleurodesis agent since 1935, a sterilization protocol has not been established. We obtained USP asbestos-free talc from six different suppliers and sterilized each using dry heat, gamma irradiation, and ethylene oxide gas. Aerobic, anaerobic, and fungal cultures were obtained prior to sterilization, and 1, 30, and 90 days after sterilization. Bacillus species were cultured from all six unsterilized specimens and coagulase-negative Staphylococcus grew from two unsterilized specimens. No growth of organisms was found following any method of sterilization. The cost of sterilization per 5-g packet of talc was $4.74, $7.85, and $16.25 for heat, ethylene oxide, and gamma irradiation, respectively. In conclusion, untreated talc is not sterile. Sterilization by prolonged dry heat exposure, ethylene oxide gas, and gamma irradiation are all effective, with dry heat being the least expensive.