During nonthyroidal illness in man and a number of experimental animals, serum total thyroid hormone levels are decreased. To determine whether the reduction in thyroid hormones that occurs during nonthyroidal illness is beneficial or harmful to the host, an experimental animal model was developed. Male Sprague-Dawley rats were infected with Streptococcus pneumoniae type I, a known human pathogen. By 40 h after inoculation, serum total and free T4 and total T3 decreased significantly. Serum free T3 also decreased slightly but not significantly. When infected animals were injected daily with T4, there was a decrease in the time to death and significant increase in the total number of deaths compared to controls receiving vehicle alone. Control experiments showed that T4 did not affect the growth of S. pneumoniae on blood agar plates, and the injected T4 did not cause hyperthyroidism. These results suggest that the decrease in serum thyroid hormone that occurs during nonthyroidal illness is beneficial and may serve a role in maintaining homeostasis by conserving metabolic energy during infection as an important adaptation that prolongs survival.