Total and free concentrations of T4 and rT3 in serum and cerebrospinal fluid were estimated by ultrafiltration in 12 patients with unipolar endogenous depression before and after electroconvulsive treatment. Recovery from depression resulted in a decrease in CSF concentrations of free T4 (median) (26.2 to 21.4 pmol/l, p less than 0.02) and free rT3 (14.1 to 12.3 pmol/l, p less than 0.05). Concentrations of free T4 in the cerebrospinal fluid were lower than those in serum (p less than 0.02), the ratio being 0.6. In contrast, levels of free rT3 in the cerebrospinal fluid were considerably higher than those found in serum (p less than 0.01), the ratio being 25. These ratios did not change following recovery from depression. In 9 patients with nonthyroidal somatic illness, concentrations of free T4 and rT3 in the cerebrospinal fluid were similar to those found in patients with endogenous depression, whereas 4 hypothyroid patients and one hyperthyroid patient had considerably lower and higher, respectively, concentrations of both free T4 and rT3. In conclusion, levels of free T4 and free rT3 in the cerebrospinal fluid are increased during depression compared with levels after recovery, probably reflecting an increased supply of T4 from serum and an increased production of rT3 from T4 in the brain. The data also suggest that the transport of iodothyronines between serum and the cerebrospinal fluid is restricted.