Antiestrogen therapy has been proposed as a treatment option for ductal carcinoma in situ (DCIS). However, its effectiveness has not been evaluated in the laboratory due to lack of an animal model. The present study was undertaken to evaluate the incidence, time span, and number of mammary glands involved with DCIS in a rat model treated with N-nitroso-N-methylurea (NMU). Sprague Dawley female rats 44 to 49 days old were treated with two iv doses of 5 mg NMU/100 g body wt given 7 days apart, initiated at diestrus. Animals were killed at intervals beginning 21 days following first injection. Breast tissues were evaluated following routine H&E stain. Standard histologic criteria were followed to establish the diagnosis of DCIS. The number of glands involved with DCIS increased from one to seven with time from first injection. This model demonstrates an incidence of 87% for DCIS and 0% for invasive Ca between 22 and 45 days following NMU injection. Nine rats were sacrificed between 50 to 60 days and five showed invasive carcinoma. This model appears suitable for studying the efficacy of hormone or chemoprevention in the progression of DCIS to invasive Ca.