Silver iontophoretic catheters (SIC) were shown to be highly efficacious in preventing catheter infections in vitro and in a rabbit model (J. Infect. Dis. 173 (1996) 495). Furthermore, we sought to determine the safety and durability of SIC prior to use in humans. A total of 30 New Zealand white rabbits (3-4 kg) were randomly assigned to one of three groups whereby SIC or Arrow Guard (AG) catheters were tunneled and inserted in the jugular vein. All animals were followed for 2-12 weeks after catheter implantation. Blood was collected from each rabbit for assessment of toxicity and determination of silver levels. The electrical current generated by each SIC was measured once daily. At the end of the follow-up period, tissue samples were collected from the skin surrounding the catheter, the lungs, spleen, and liver. Microscopically, none of the tissues examined from any of the animals showed evidence of silver deposits, silver toxicity, thermal or electrical injury. The silver levels in the animals that received the SIC ranged from 0.1 to 2.23 microg/l with a mean of 0.62 (+/-0.44 SD). In conclusion SIC were safe with normal serum silver levels and were not associated with any local or systemic toxicity.