The effects of a HF diet on male DO mice were evaluated after 14 weeks on the diet.  Mice were fed ad libitum, except during designated fasting periods, either a control diet (10 kcal % fat; D12450J) or a HF diet (60 kcal %; D12492) (Research Diets, New Brunswick, NJ) at the start of the study.  Serum insulin and leptin were determined one week prior to the start of the study and at week 14 at terminal sacrifice.  Blood glucose was measured one week prior to the start of the study and during weeks 5, 9 and 14 using a Blood Glucose Monitoring System Meter.  At termination, body, liver, brain, kidney, testes, and epididymis were weighed.  Epididymal sperm motility and concentration parameters were measured by computer-assisted sperm analysis (CASA, Hamilton-Thorne, Beverly, MA) per NTP specifications. Upon arrival, mice weighed approximately 23.6 ± 2.9 g.  After 14 weeks mice on the high fat diet weighed approximately 30% more than animals on the control diet (43.8 g vs 33.2 g, respectively).   Mice on the HF diet gained more than twice as much weight as the controls (20.2 g vs 9.7g, respectively).  Approximately ¼ of the mice on the HF diet had blood glucose levels equivalent to the controls and approximately ¼ of the mice had blood glucose levels twice the controls.   The most striking observation was the 70 fold range in sperm counts in the DO mice.  In comparison, at the NTP, sperm count varies no more than 2 fold within a study in the B6C3F1 mice.  Approximately ¼ of the mice on the HF diet did not differ from controls in body weight or clinical chemistry.  Compared to the B6C3F1 mice typically used at the NTP, the coefficient of variation for organ and body weights is approximately 3-6 times higher in the DO mice.   Using power calculations (80% power at p< 0.05), studies using the DO mice would require 25-34 mice to be equally powered as a typical subchronic study using the B6C3F1 mouse.  However, due to the variability in sperm counts in the DO, it would require 150 mice/group to have the same power as 10 mice/group of the B6C3F1 strain.  This study demonstrates that for some endpoints the DO mice vary greatly, while other endpoints the variance is slightly higher than the B6C3F1 mouse.