Experience with the use of simultaneous oral and iv radioiodine tracers of thyroxine (T4) to measure T4 absorption was reviewed to determine the effect of advanced age on T4 absorption and to search for acceptable simplifications in the measurement methodology. (1) Age effect: In control subjects, T4 absorption did not differ with age between 21 and 69 years; it averaged 62.8 +/- 13.5% (SD) in subjects over age 70 compared with 69.3 +/- 11.9% in subjects aged 21-69 (p < 0.001). We conclude that, because of this small but significant reduction in T4 absorption efficiency in the elderly, it is especially important to monitor individual response to replacement T4 doses in this age group. (2) Methodology studies: Intrasubject coefficient of variation for T4 absorption in triplicate studies averaged 8.9%, when an identical method was used at weekly intervals (n = 3). When the 3 studies were done by 3 separate methods (sequential po and i.v. 123I-labeled T4, sequential 125I-labeled T4 po and i.v., and simultaneous po and i.v. doses of different tracers), the intrasubject coefficient of variation averaged 9.8% (n = 8). When the absorption calculation used only one serum sample, taken after isotopic equilibrium was achieved at 24 h [the double isotope (eq) method], calculated T4 absorption differed little from that calculated in the same subjects using a full serum time-activity curve and a noncompartmental analysis [the double isotope (AUC) method]. Compared with a compartmental model solution, both methods slightly overestimated T4 absorption. In 4 subjects given i.v. radioiodide as a third tracer at the same time demonstrated that, as long as radioiodide contamination of the T4 tracers is measured and accounted for in the standards, contaminating radioiodide has no clinically significant effect on T4 absorption measurements. When an oral tracer of T4 was considered alone, without an i.v. tracer to correct for T4 metabolism, the estimates of T4 absorption correlated in a curvilinear fashion with T4 absorption as measured by the double isotope method. Except at very low absorption levels, the oral tracer alone is a poor predictor of T4 absorption. We conclude that, when using a double isotope method to measure T4 absorption, it is acceptable to rely on a single serum sample taken at 24 h, a time when isotopic equilibrium between the two tracers has been reached.(ABSTRACT TRUNCATED AT 400 WORDS)