Previous studies with Lewis/Brown-Norway (BN) F1 hybrid rats indicated that spermatogenesis was much more sensitive to ionizing radiation than in the widely studied outbred Sprague Dawley stock, suggesting that there were genetically based differences; however, the relative sensitivities of various inbred strains had not been established. As a first step to defining the genes responsible for these differences, we compared the sensitivities of seven rat strains to radiation damage of spermatogenesis. Recovery of spermatogenesis was examined 10 weeks after 5-Gy irradiation of seven strains (BN, Lewis, Long-Evans, Wistar Kyoto, spontaneously hypertensive [SHR], Fischer 344, and Sprague Dawley). The percentages of tubules containing differentiated cells and testicular sperm counts showed that BN and Lewis were most sensitive to radiation (< 2% of tubules recovered, < 2 × 10(5) late spermatids per testis), Long-Evans, Wistar Kyoto, Fischer, and SHR were more resistant, and Sprague Dawley was the most resistant (98% of tubules recovered, 2 × 10(7) late spermatids per testis). Although increases in intratesticular testosterone levels and interstitial fluid volume after irradiation had been suggested as factors inhibiting recovery of spermatogenesis, neither appeared to correlate with the radiation sensitivity of spermatogenesis in these strains. In all strains, the atrophic tubules without differentiated germ cells nevertheless showed the presence of type A spermatogonia, indicating that their differentiation was blocked. Thus, we conclude that the differences in radiation sensitivity of recovery of spermatogenesis between rat strains of different genetic backgrounds can be accounted for by differences in the extent of the radiation-induced block of spermatogonial differentiation.