Objective-To evaluate effects of commonly used anesthetics administered as single bolus injections on splenic volume. Animals-10 adult Beagles. Procedures-A randomized crossover study was conducted. Computed tomography was performed on dogs to determine baseline splenic volume and changes after IV injection of assigned drug treatments. Dogs were allowed to acclimate for 10 minutes in a plastic crate before acquisition of abdominal CT images. Treatments were administered at 7-day intervals and consisted of IV administration of saline (0.9% NaCl) solution (5 mL), acepromazine maleate (0.03 mg/kg), hydromorphone (0.1 mg/kg), and dexmedetomidine (0.005 mg/kg) to all 10 dogs; thiopental (8 mg/kg) to 5 of the dogs; and propofol (5 mg/kg) to the other 5 dogs. Splenic volume was calculated from the CT images with image processing software. A repeated-measures ANOVA was performed, followed by a Bonferroni post hoc test. Results-No significant difference in splenic volume was detected between the acepromazine, propofol, and thiopental treatments, but splenic volume was greater with these drugs than with saline solution, hydromorphone, and dexmedetomidine. Splenic volume was less with hydromorphone, compared with dexmedetomidine, but splenic volume with hydromorphone and dexmedetomidine did not differ significantly from that with saline solution. Conclusions and Clinical Relevance-Administration of acepromazine, thiopental, and propofol resulted in splenomegaly. Dexmedetomidine did not alter splenic volume. Hydromorphone slightly decreased splenic volume. Propofol should not be used when splenomegaly is not desirable, whereas hydromorphone and dexmedetomidine may be used when it is best to avoid splenic enlargement.