This secondary-level animal study was conducted to assess and compare the subcutaneous tissue reaction to implantation of white mineral trioxide aggregate (MTA) and white Portland cement. Polyethylene tubes filled with either freshly mixed white MTA (Group I) or white Portland cement (Group II) were implanted subcutaneously into 12 Wistar Albino rats. Each animal also received an empty polyethylene tube as the control (Group III). After 7, 14, 21 and 30 days, the implants, together with surrounding tissues were excised. Two pathologists blinded to the experimental procedure, evaluated sections taken from the biopsy specimens for the severity of the inflammatory response, calcification and the presence and thickness of fibrous capsule surrounding the implant. Statistical analysis was performed using the Cross-tabs procedure, Univariate analysis of the variance two-way and the Pearson product moment correlation to assess inter-rater variability between the two evaluators. At 7 days, there was no significant difference in the severity of inflammation between the control group, white MTA, and white Portland cement groups. In the 14 day, 21 day and 30 day test periods, control group had significantly less inflammation than white MTA and white Portland cement. There was no significant difference in the grading of inflammation between white MTA and white Portland cement. All materials exhibited thick capsule at 7 days and thin capsule by 30 days. Both white MTA and white Portland cement were not completely non-irritating at the end of 30 days as evidenced by the presence of mild inflammation. However, the presence of a thin capsule around the materials, similar to the control group, indicates good tissue tolerance. White MTA and white Portland cement seem to be materials of comparable biocompatibility.