Abstract.Serum lipids and apolipoproteins (apo) A‐I, A‐II, and B were measured in twenty‐four patients with severe primary hypothyroidism (Thyrotropin above 40 mU/l), before and during l‐thyroxine treatment. Apo A‐I, A‐II, and B were assayed by immunonephelometry, using monospecific antisera.The serum levels of total cholesterol (TC), of low‐density lipoprotein cholesterol (LDLc), and of the major LDL apoprotein, apo B, were markedly increased in the untreated hypothyroid patients compared to the values during therapy (TC: mean±SD, 8·87±2·9v.5·48±1·6 mmol/l; LDLc: 6·66±2·6v.3·78±1·4 mmol/l; apo B: 1·66±0·48v.1·14±0·37 g/l;P<0·00001 for all variables). High‐density lipoprotein cholesterol (HDLc) was slightly higher before than during therapy (1·58±0·7v.1·31±0·4 mmol/l;P<0·05), while the main HDL apoprotein, apo A‐I, was significantly elevated (1·49±0·42v.1·13±0·27 g/l;P<0·0002). The increase of the second major HDL apoprotein, apo A‐II, was less pronounced (0·33±0·1v.0·30±0·08 g/l;P<0·022). The apo A‐I to apo A‐II ratio, which reflects the relative concentrations of the HDL subfractions HDL2and HDL3, was significantly higher before than during treatment (P<0·0006). Serum triglyceride levels were moderately elevated in the untreated hypothyroid patients (1·34±0·6v.0·95±0·4 mmol/l;P<0·002). The small decrease in body weight during therapy did not correlate with the changes of the various lipid and apoprotein parameters.These data indicate that severe hypothyroidism has a differential influence on the serum concentrations of the major HDL apoproteins, A‐I and A‐II, and sugges