Following a recently reported rise in serum reverse triiodothyronine levels in response to cold exposure, an initial in vitro study has been carried out on human lymphocyte function. The first part of the study demonstrated that the uptake of rT3 on lymphocyte nuclear receptors increased as the rT3 concentration was raised above the normal serum level. The binding is competitive with triiodothyronine. The lymphocytes were harvested from venous blood donated by young male U.S. naval personnel. The second part of the study involved lymphocyte proliferation assays carried out with the addition of increasing amounts of rT3. Both non-specific (three different mitogens) and specific (recall antigen) stimuli were used. There was an indication that lymphocyte function is depressed by increasing serum concentration of rT3. However, with a small number of test subjects and a resulting low statistical power, it was not possible to establish a statistically significant association. Lymphocytes from umbilical cord blood, which has a very high level of rT3 compared to that in normal adult sera, were also found to have a much reduced lymphocyte stimulation index. The requirements for a more definitive investigation are outlined.