Testosterone administration to men is known to decrease high-density lipoprotein cholesterol (HDL-C) and the subclasses HDL₂and HDL₃. It also might increase the number of small, dense, low-density lipoprotein cholesterol (LDL-C) particles in hypogonadal men. The decrease in HDL-C and in LDL-C size is potentially mediated by hepatic lipase activity, which hydrolyzes lipoprotein phospholipids and triacylglycerol. To determine how HDL-C and LDL-C particles are affected by testosterone administration to eugonadal men, testosterone was administered as a supraphysiological dose (600 mg/wk) for 3 wk to elderly, obese, eugonadal men before elective hip or knee surgery, and lipids were measured by routine methods and by density gradient ultracentrifugation. Hepatic lipase activity increased >60% above baseline levels, and HDL-C, HDL₂, and HDL₃significantly declined in 3 wk. In addition, the LDL-C peak particle density and the amount of LDL-C significantly increased. Testosterone is therefore a potent stimulator of hepatic lipase activity, decreasing HDL-C, HDL₂, and HDL₃as well as increasing LDL particle density changes, all associated with increased cardiovascular risk.