This study examined the role of cholesteryl ester transfer (CET), cholesteryl ester transfer protein (CETP) activity, and phospholipid transfer protein (PLTP) activity in the increased prevalence of coronary artery calcification (CAC) in diabetic subjects compared with nondiabetic subjects and in the loss of the sex difference in CAC in diabetes. CETP activity, PLTP activity, and CET were measured in 195 type 1 diabetic subjects without renal failure and 194 nondiabetic control subjects of similar age (30-55 years) and sex distribution (50% female). CAC was quantified with electron beam computed tomography. CETP activity was higher in diabetic subjects (mean 84 arbitrary units [AU]) than in nondiabetic subjects (80 AU, P = 0.028). PLTP activity was also higher in diabetic subjects (96 AU) than in nondiabetic subjects (81 AU, P <0.001). However, CET was lower in diabetic men (geometric mean 32 nmol. ml-1.h-1) than nondiabetic men (37 nmol.ml-1.h-1, P = 0.004) and did not differ between diabetic (30 nmol. ml-1.h-1) and nondiabetic (32 nmol.ml-1.h-1, P = 0.3) women. CETP and PLTP activities were not associated with CAC. CET was positively associated with CAC in both diabetic and nondiabetic subjects (odds ratio per 10 nmol.ml-1.h-1 increase in CET in all subjects = 1.4, P = 0.001). The prevalence of CAC was similar in diabetic (51%) and nondiabetic (54%, P = 0.7) men but was much higher in diabetic (47%) than nondiabetic (21%, odds ratio 3.6, P <0.001) women so that there was no sex difference in CAC in diabetic subjects. The odds of CAC in diabetic women compared with nondiabetic women was altered little by adjustment for CETP activity, PLTP activity, or CET (odds ratio on adjustment 3.7, P <0.001). The greater effect of diabetes on CAC in women than in men, i.e., the loss of the sex difference in CAC, was independent of CETP and PLTP activity and CET. In conclusion, among both diabetic and nondiabetic subjects, higher cholesteryl ester transfer is a risk factor for CAC. However, abnormalities in cholesteryl ester transfer or lipid transfer protein activities do not underlie the increased CAC risk in diabetic women compared with nondiabetic women or the loss of the sex difference in CAC in diabetes.