The effects of low-dose short-term corticosteroids on plasma lipid and lipoprotein cholesterol was measured in 23 subjects who received prednisone for active rheumatic disease. After 1 month, plasma cholesterol increased from 195 to 219 mg/dl (P less than 0.001), and high density lipoprotein cholesterol (HDL-C) from 52 to 70 mg/dl (P less than 0.001). Mean plasma triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) did not show a significant change. There was a wide variation in individual response of plasma lipid values to corticosteroid treatment. There was also a strong relationship between change in plasma total cholesterol and change in LDL-C (r = 0.86) (P less than 0.001), and change in TG (r = 0.39, P less than 0.01), but not in HDL-C. Thus, short-term, low-dose corticosteroids markedly affect plasma lipid levels. In most subjects there is an increase in HDL-C; however, an increase in total cholesterol may be indicative of a change in VLDL-C and LDL-C as well.