The efficacy and clinical safety of chlormadinone acetate (CAP) in preventing estrus were assessed in bitches on condition that CAP was subcutaneously implanted in silastic silicon rubber. To evaluate the long-term efficacy of implantation, 19 bitches were divided into 4 groups given doses of 2.5, 5, 10 and 25 mg/kg, respectively. Although estrus was observed within 13 months after implantation in all of the bitches given CAP in the 2.5 mg/kg dose, and in 13 to 15 months in 3 of the 5 bitches given the 5 mg/kg dose, it was prevented for at least 24 months in all of the bitches given doses of 10 mg/kg or more. Plasma progesterone levels remained low throughout the period of estrus prevention, indicating a close correlation with the effect of CAP. The mean body weight of the bitches in groups receiving higher doses increased slightly over the course of the experiment. Except this, no clinical, hematology or biochemistry abnormalities were found in any of the treated bitches. Another 6 bitches were given 10 to 30 mg/kg of CAP, but the implants were removed to observe the recurrence of estrus and to measure the amount of CAP in the removed implant. Estrus recurred after removal even in the bitch given 30 mg/kg. The concentrations of CAP in the plasma and the amounts of CAP remaining in the implants demonstrated the sustained release of CAP from the implants. The concentrations of CAP in the individual bitches indicated that the lowest concentration effective in preventing estrus is 0.7 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)