Because wild rodents often harbor zoonotic pathogens that can be transmitted via saliva, urine, or feces (e.g., hantaviruses), researchers can be at risk when collecting rodent blood or tissue samples that are required for innumerable assays (e.g., infection status, hormone assays, etc.). I describe how inexpensive, readily available 50-mL centrifuge tubes can be easily modified to create a handling tube for the safe restraint of small rodents while a blood and/or tissue sample is collected from the tail. This approach has been used to successfully sample thousands of deer mice (Peromyscus maniculatus), the primary host for Sin Nombre virus, a zoonotic disease that is pathogenic for humans.