A silk thread (0-0) or a copper wire (0.18 mm diameter) was placed in the left uterine horn of rats, at least 3 days before fertilization. The animals were untreated or given daily injections of 3 mgh hydrocortisone or 30 mg aspirin beginning the day after insertion of the IUD; 2 weeks after coitus, the animals were killed. A longitudinal (less than or equal to 10 mm) silk thread and the copper wire were effective IUDs regardless of treatment. With the short silk thread (less than or equal to 2 mm), implantation occurred in all groups of rats but a high failure rate was observed in hydrocortisone-treated rats (5/9 with implantations). The no. of implantations/no. of corpora lutea (x 100) was much higher (20.4%) in rats treated with aspirin and hydrocortisone than in untreated animals (3.2%) (P less than 0.01). We conclude that the effectiveness of an IUD can be altered by treatment with an anti-inflammatory substance.