To determine the age-related changes in thyroid hormone (TH) effects on cardiac glucose transporter one (GLUT-1) and four (GLUT-4) isoforms, male Fischer 344 rats at 4, 12, and 25 months of age were studied at euthyroid, hyperthyroid and hypothyroid conditions. Hyperthyroidism was induced with daily intraperitoneal injections of triiodothyronine (15 microg/100 gm) for 10 days. Hypothyroidism was achieved with 0.025% methimazole in the drinking water for 4 weeks. Immunoblot analysis indicated that at euthyroid basal conditions GLUT-1 protein was not significantly altered with age while GLUT-4 protein was significantly reduced in 25 month old rats (82.0 +/- 28.8% of a 4 month old rat p <0.01). In 4 months old rats, GLUT-1 was increased in both hypothyroidism (432.5 +/- 208.7% of age-matched euthyroid control) and to a lesser extent in hyperthyroidism (242.0 +/- 93.3% of control) p<0.01. In 25 month old rats, hyperthyroidism was also associated with increased GLUT-1 mass (190.8 +/- 117.6% of age-matched euthyroid control) p<0.01. Hypothyroidism in this age group was not associated with significant change in GLUT-1 protein. The cardiac GLUT-4 protein was increased during both hypothyroidism and hyperthyroidism. The changes of GLUT-4 in aged rats were similar to those found in young rats. It is concluded that TH effect on GLUT-1 expression in the heart is altered with age while TH effects on GLUT-4 are age independent.