In this paper, we present the novel design features, their technical implementation, and an evaluation of the radio frequency exposure systems developed for the National Toxicology Program (NTP) of the National Institute of Environmental Health Sciences studies on the potential toxicity and carcinogenicity of second and third generation mobile-phone signals. The system requirements for this second-year NTP cancer bioassay study were the tightly controlled lifetime exposure of rodents (1568 rats and 1512 mice) to three power levels plus sham simulating typical daily, and higher, exposures of users of GSM and CDMA (IS95) signals. Reverberation chambers and animal housing were designed to allow extended exposure time per day for free-roaming individually housed animals. The performance of the chamber was characterized in terms of homogeneity, stirred to unstirred energy and efficiency. The achieved homogeneity was 0.59 and 0.48 dB at 900 and 1900 MHz, respectively. The temporal variation in the electric field strength was optimized to give similar characteristics to that of the power control of a phone in a real network using the two stirrers. Experimental dosimetry was performed to validate the SAR sensitivity and determine the SAR uniformity throughout the exposure volume; SAR uniformities of 0.46 and 0.40 dB, respectively, for rats and mice were achieved.