The concentrations of lipids and apolipoproteins in serum from men with chronic schizophrenia who were receiving major tranquilizers (17 receiving phenothiazines and 14 receiving a butyrophenone) were quantitated and compared with serum from male controls (n = 14). Concentrations of high-density lipoprotein cholesterol and apolipoproteins A-I and A-II were significantly lower in the patients than in the controls. Mean apolipoproteins C-II and C-III and very low-density lipoprotein cholesterol levels in the patients receiving phenothiazines were higher than levels in the patients receiving butyrophenone or in the controls. There were no significant differences in levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or apolipoproteins B and E. The triglyceride level in patients receiving phenothiazines (163 +/- 65 mg/dl) was higher than that in patients receiving butyrophenone (104 +/- 52 mg/dl). Our data suggest that, with respect to triglyceride metabolism, butyrophenone is more beneficial than are phenothiazines.