We recently have reported that patients with hyperthyroidism have red blood cell carbonic anhydrase I (CAI) levels that reflect the patient's integrated thyroid hormone level over the preceding few months. In the present study, the effect of T3 on CAI concentrations in the human erythroleukemic cell line, YN-1, was studied. The presence of high affinity (1.9 x 10(9) L/mol), low capacity (20.4 fmol/10(6) cells) T3 binding sites was demonstrated in YN-1 cell nuclei. T3 at a physiological free T3 concentration (0.54 nmol/L) significantly (32 +/- 7%, P < 0.01) decreased CAI concentrations in YN-1 cells before induction of differentiation. The effect of T3 on CAI levels was more obvious (42 +/- 7%, P < 0.01) in the presence of transforming growth factor-beta 1 (TGF-beta 1), which induces hemoglobin synthesis and differentiation in YN-1 cells. These results suggest that the YN-1 cell line may be used to study T3 action on human red blood cell CAI.