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