Low density lipoproteins labeled with [125I]tyramine cellobiose ([125I]TC-LDL) were removed from the circulation of squirrel monkeys at a similar but slightly slower rate than LDLs labeled with 125I, [125I]hydroxyphenyl propionic acid, or [3H]leucine. After the simultaneous injection of [125I]TC-LDL and [131I]LDL labeled with 131ICl, the 125I was also removed at a slightly slower rate than 131I. Most of the radioactivity was retained in tissues and not excreted during the 24 h after injection of [125I]TC-LDL. This finding supports the claim of Pittman et al. [18] that [125I]TC-LDL can be used to determine the irreversible uptake of LDL by different tissues. The liver cleared more LDL than any other organ, but the adrenals and ovaries were more active per gram. Trichloroacetic acid (TCA) precipitated more than 80% of the radioactivity in the tissues that had low 125I uptake, but only about 50% of the 125I in more active tissues (liver, adrenals, ovaries, and spleen). Only a small percentage of 125I in urine and bile was TCA-precipitable. In the dual label experiment with [125I]TC-LDL and [131I]LDL there was a selective retention of 125I in samples from liver, spleen, adrenals, and, perhaps testes, and an almost complete selectivity for 125I in bile and feces. The aortic intima plus inner media (AIM) cleared much less LDL than other tissues, but the uptake by the entire AIM was proportional to the cholesterol concentration and weight of the total AIM. There was, however, no correlation between either of the latter two measurements and the uptake of LDL per gram of AIM. The concentration of LDL apolipoprotein in the AIM determined by immunoelectrophoresis did not correlate significantly with LDL uptake per gram. Both the amounts of LDL apolipoprotein present and labeled LDL taken up by the AIM depended on the weight of the sample, and perhaps on the weight of intima in the sample.