The hypothesis was investigated that colloidal ferric or aluminum hydroxides, formed in blood plasma in vivo, potently absorb lead and thus profoundly influence uptake of lead into certain soft tissues. Rats were given 203Pb i.v. to obtain a near constant plasma level of 203Pb. Tissue uptake of 203Pb at 1 hr was determined with and without the i.v. infusion of 5.0 mM ferric chloride or 5.0 mM aluminum chloride. Infusion of Fe chloride or Al chloride suppressed the uptake of 203Pb into brain, cerebrospinal fluid, skeletal muscle, kidney and red cells by 70 to 94%. In contrast, the uptake of 203Pb into liver and spleen was not significantly reduced, in the case of spleen being greater after Fe chloride or Al chloride infusion. The latter increases were not statistically significant. After ultracentrifugation, greater than 70% of plasma 203Pb activity was associated with the hydroxide-protein pellet (Fe chloride and Al chloride experiments). The ultrafilterable 203Pb in such sera was reduced by greater than 90% compared with controls. By the use of the lead electrode in vitro, lead adsorption to ferric hydroxide was confirmed. Thus, in vivo formation of colloidal hydroxides must occur under the authors' conditions, leading to a reduction of ionized lead in plasma and lower uptake where this depends on free lead and comparable or enhanced uptake into tissues containing reticuloendothelial cells capable of phagocytosis.