The relation of plasma lipids and pseudocholinesterase (PChE) activity was studied in rats made hypothyroid by treatment with propylthiouracil (0.05% in drinking water for 28 days) and in hypothyroid patients prior and after L-thyroxine-therapy (1. week 25-50 microg, 2.-4. week 100 microg daily). In rats, thyroid hormone deficiency caused a significant increase in plasma and adipose tissue PChE activity as well as total plasma cholesterol (TC) concentration, and a decrease in plasma triglyceride (TG) concentration. In contrast to rats, thyroid-deficient humans demonstrated a decrease in plasma PChE activity and an increase in both TC and TG, in comparison with euthyroid controls. After one month's therapy with L-thyroxine, reversion of PChE activity and lipid concentrations occurred. The opposite changes of PChE elicited by thyroid hormone deficiency in men and rats are similar to the respective changes in lipoprotein lipase (LPL) activity, observed by other authors. The inverse correlation between both PChE and LPL activity and TG concentration suggests that PChE, similarly to LPL, may be involved in TG hydrolysis.