Reduced plasma levels of high density lipoprotein cholesterol (HDLC) and apolipoprotein A-I (apoA-I) are both indicators of increased risk of developing coronary artery disease. We have used autologous 125-I-HDL to determine the rates of production (PR) and fractional catabolism (FCR) of apoA-I, the major, structural apolipoprotein in HDL, in three groups of men that included the following: four normal subjects (triglyceride [TG] = 61.0 +/- 5.0 mg/dL, HDLC = 51.5 +/- 7.0 mg/dL), four subjects with both hypertriglyceridemia and reduced HDLC (TG = 360.3 +/- 111.1 mg/dL, HDLC = 23.8 +/- 6.1 mg/dL), and seven subjects with only reduced HDLC (TG = 103.7 +/- 49.5 mg/dL, HDLC = 25.6 +/- 6.1 mg/dL). In the group with both the high TG and low HDL, apoA-I PR was significantly greater than the apoA-I PR in the normal group (14.2 +/- 2.3 v 10.6 +/- 1.9 mg/kg.d, P less than .05). ApoA-I FCR was also significantly greater in the former group v normals (0.38 +/- 0.08 v 0.21 +/- 0.04 d-1, P less than .02). In contrast, the group of subjects with only low HDLC had a significantly lower apoA-I PR v the normal subjects (7.1 +/- 2.0 v 10.6 +/- 1.9 mg/kg.d; P less than .05). ApoA-I FCR was variable in the group with isolated low HDLC, but the mean FCR was not different from normal (0.26 +/- 0.09 v 0.21 +/- 0.04 d-1).(ABSTRACT TRUNCATED AT 250 WORDS)