The impact of acute infection on thyroid physiology was investigated in rats infected with a type-specific pneumococcus. Infected rats showed a lower thyroidal 131I uptake than healthy controls at all time periods studied. Unlike in the rat, thyroidal 131I uptake curves in the infected and healthy mouse and guinea pig were superimposable. Thyroidal 131I release in the infected rat was significantly delayed when compared to similar release curves in uninfected animals. Although the thyroid of the infected rat responded to a physiologic dose of exogenous TSH, both its uptake and release of 131I showed an absolute reduction. Serum TSH levels measured by bio-assay were not altered during infection. The disappearance time of 131I-T4 from blood of infected rats was significantly shorter than that of healthy controls, while disappearance times of blood 131I-T3 were unchanged. Organ radioactivity was measured following serial sacrifice after the administration of 131I-T4 or 131I-T3 to healthy and infected rats. In the T4 group radioactivity in livers from infected rats was consistently lower than in healthy animals.