Sulfolane is a widely used industrial solvent that is often used for gas treatment (sour gas sweetening; hydrogen sulfide removal from shale and coal processes, etc.), and in the manufacture of polymers and electronics, and may be found in pharmaceuticals as a residual solvent used in the manufacturing processes. Sulfolane is considered a high production volume chemical with worldwide production around 18 000–36 000 tons per year. Given that sulfolane has been detected as a contaminant in groundwater, an important potential route of exposure is tap water ingestion. Because there are currently no federal drinking water standards for sulfolane in the USA, we developed a noncancer oral reference dose (RfD) based on benchmark dose modeling, as well as a tap water screening value that is protective of ingestion. Review of the available literature suggests that sulfolane is not likely to be mutagenic, clastogenic or carcinogenic, or pose reproductive or developmental health risks except perhaps at very high exposure concentrations. RfD values derived using benchmark dose modeling were 0.01–0.04 mg kg⁻¹ per day, although modeling of developmental endpoints resulted in higher values, approximately 0.4 mg kg⁻¹ per day. The lowest, most conservative, RfD of 0.01 mg kg⁻¹ per day was based on reduced white blood cell counts in female rats. This RfD was used to develop a tap water screening level that is protective of ingestion, viz. 365 µg l⁻¹. It is anticipated that these values, along with the hazard identification and dose–response modeling described herein, should be informative for risk assessors and regulators interested in setting health-protective drinking water guideline values for sulfolane.