We studied the acute effect of standard therapeutic doses of oral frusemide on indices of thyroid function in 34 hospital in-patients with congestive cardiac failure. A transient decrease in total T4, elevation in the T3 resin uptake and consequent increase in the free T4 index (FT4I) were seen 2-5 h after ingestion of frusemide at a chronic morning dosage of 80, 120 or 250 mg. The FT4I pre-vs post-frusemide values after 250 mg of drug were 109 +/- 12 vs 129 +/- 18 (P less than 0.05) after 120 mg 92 +/- 14 vs 119 +/- 12 (P less than 0.01), and after 80 mg 102 +/- 6 vs 112 +/- 4 (P less than 0.01) (mean +/- SEM). Similar increases in apparent free T4 measured by an analogue tracer assay (free T4 RIA sol, Henning, Berlin) were seen after frusemide. In a time course study, the major change in the T3 uptake 120 min after frusemide ingestion correlated with the change in serum frusemide concentration. When frusemide was added to serum in vitro its influence was greatest in methods that involved least dilution of serum. In two of the patients difficulty in clinical assessment of thyroid status was compounded by the effect of oral frusemide on FT4I. We conclude that oral frusemide may influence biochemical assessments of thyroid function in patients with congestive cardiac failure. It is necessary to consider the time interval between ingestion of high doses of oral frusemide and blood sampling in evaluating such results.