Studies have shown that plasma albumin fractions (PAFs) from hibernating mammals can inhibit induced contractility of the guinea pig ileum similarly to morphine. This study examined PAFs from two species of prairie dogs, one that undergoes natural seasonal hibernation (white-tailed, WT) and one that does not but can be induced to hibernate (black-tailed, BT). Dose-response curves of lyophilized PAF yielded IC50 values (mg) of 20.23 for summer WT, 15.53 for hibernating WT, 15.45 for summer BT, and 13.16 for winter-active BT. Winter samples from both species have IC50s lower than samples from summer animals, indicating greater potency of winter PAFs in suppressing guinea pig ileum contractility and therefore the presence of more opioid ligands in winter prairie dog plasma. Studies to elucidate receptor selectivity of PAF continue.