In tissue culture, protection against X irradiation by a number of cysteamine derivatives was studied and the results were compared with data obtained in mice. Compounds with a covered SH group, like WR 638, cysteamine phosphate, WR 2721 and AE AE 48527, showed practically no protection when dissolved in tissue culture medium, but developed a protective activity wehn dissolved in rat blood. Thiol measurements demonstrated that in rat blood the compounds were partly hydrolysed to thiols. C511 was also hydrolysed in culture medium and was slightly less effective than cysteamine in culture medium. Cysteamine phosphate was hydrolysed more easily than cysteamine sulphate and the protective activity in rat blood was better. WR 2721 was also partly hydrolysed in rat blood. The in vitro protection of this compound was disappointing when compared with results in vivo. Its SH form (WR 1065) also showed less protection than expected from in vivo experiments. Thus, the little protection by WR 2721 in vitro in rat blood is not only due to its incomplete conversion into its thiol. Longer incubation times and the use of rat blood as a solvent brought the protective activity of WR 1065 almost up to the level of cysteamine. This may indicate that WR 1065 penetrates the cells poorly. WR 1065 was the only compound we studied whose protective activity in vitro was improved appreciably by dissolving it in rat plasma. Chemicals/CAS: 2 (3 aminopropylamino)ethanethiol, 14653-77-1, 31098-42-7; amifostine, 20537-88-6; cystafos, 3724-89-8; cystamine, 51-85-4, 56-17-7; mercaptamine, 156-57-0, 60-23-1; thiol derivative, 13940-21-1; Amifostine, 20537-88-6; Culture Media; Cystamine, 51-85-4; Cysteamine, 60-23-1; Mercaptoethylamines; Organothiophosphorus Compounds; Radiation-Protective Agents