To investigate the effect of sex and diabetes on postprandial lipoprotein metabolism, 15 normal and 12 normolipidemic subjects with insulin-dependent diabetes mellitus (IDDM) were studied. Plasma triglyceride (TG) levels were measured and three TG-rich lipoprotein subfractions (Sf > 400, 100 to 400, and 20 to 100) were isolated and their composition analyzed before and every 1.5 hours for a total of 7.5 hours following ingestion of corn oil. Normal women compared with men had lower postprandial plasma TG levels (P < .05) mostly due to lower TG in Sf 100 to 400. The composition of Sf 100 to 400 and Sf 20 to 100 lipoproteins differed in the two sexes (P < .01), with normal women having particles poorer in TG in both the fasting and postprandial states. Diabetic men compared with normal men had smaller Sf > 400 particles following fat ingestion, as shown by a lower TG protein (PR) ratio (7.6 v 12.8, respectively, P < .05). The composition of Sf 100 to 400 and 20 to 100 lipoproteins was abnormal in IDDM men due to enrichment in total cholesterol (TC) as shown by higher TC TG, TC PR, and TG/phospholipid (PL) ratios in both the fasting (P < .03 to P < .003) and the postprandial state (P < .03 to P < .0001). A lower PL and TG content was also consistently present. A similar enrichment in TC was observed in diabetic v normal women following fat ingestion in Sf > 400 only (P < .003). The composition of both fasting P < .04) and postprandial (P < .0001) Sf 20 to 100 lipoproteins was abnormal in diabetic women due to a higher TG and a lower PL content. When diabetic men and women were compared, there were sex differences in the composition of all three subfractions in the postprandial state. In Sf > 400 (P < .025) an enrichment in TC was present in IDDM women, whereas in Sf 100 to 400 (P < .025) an enrichment in PL was observed. Finally, in Sf 20 to 100 an enrichment in TG was present in diabetic women in both the postprandial (P < .0003) and the fasting (P < .03) states. In conclusion, there are sex differences in postprandial lipoprotein metabolism in both normal and IDDM subjects. The diabetic state is associated with TC enrichment of TG-rich lipoproteins, which could be atherogenic. In IDDM men TC enrichment was present in Sf 100 to 400 and 20 to 100 lipoproteins both in the fasting and in the postprandial state. However, in IDDM women TC enrichment was present only in intestinally produced lipoproteins (Sf > 400).