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Recent reports have claimed that institutional review boards (IRBs) are underfunded, yet little is known about the costs of operating IRBs. This study estimated the costs for operating high-volume and low-volume IRBs.IRB costs were calculated from published summary data. Costs were standardized to reflect 2001 dollars.Total estimated costs for operating high-volume and low-volume IRBs were $770,674 and $76,626, respectively. The average cost per action, a measure of economic efficiency, was lower for high-volume IRBs ($277 per action) than it was for low-volume IRBs ($799 per action).Although high-volume IRBs are more expensive than are low-volume IRBs in absolute terms, they are more economically efficient. Policy debates should consider the potential savings from large IRBs, perhaps by encouraging small IRBs to merge, although this may result in less local review, control, and oversight.