The therapeutic potential of radionuclides that emit alpha particles, as well as their associated health hazards, have attracted considerable attention. The 224Ra daughters 212Pb and 212Bi, by virtue of their radiation properties which involve emission of alpha and beta particles in their decay to stable 208Pb, have been proposed as candidates for radioimmunotherapy. Using mouse testes as the experimental model and testicular spermhead survival as the biological end point, the present work examines the radiotoxicity of 212Pb and its daughters. When 212Pb, in equilibrium with its daughters 212Bi, 212Po and 208Tl, was administered directly into the testis, the dose required to achieve 37% survival (D37) was 0.143 +/- 0.014 Gy and the corresponding RBE of the mixed radiation field was 4.7 when compared to the D37 for acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210Po, was used to obtain an RBE-LET relationship for alpha particles emitted by tissue-incorporated radionuclides: RBE alpha = 4.8 - 6.1 x 10(-2) LET + 1.0 x 10(-3) LET2. Similarly, the dependence of RBE on alpha-particle energy E alpha was given by RBE alpha = 22 E(-0.73) alpha. These relationships, based on in vivo experimental data, may be valuable in predicting biological effects of alpha-particle emitters.