Reliable and safe methods of reversible contraception are needed for use in zoo felids. The efficacy of levonorgestrel (LNG) as a contraceptive, when delivered as a cesium-irradiated, slow-release, injectable matrix, was tested in domestic cats as a model for exotic cats. An increase (P = 0.0017) in body weight was observed in treated but not control queens (P = 0.2146). All control queens (n = 6), which received injections of matrix only, but none of the LNG-treated queens (n = 6) became pregnant during the trial. Levonorgestrel was effective in preventing pregnancy for at least 36 weeks after two injections of drug-loaded formulations (40 mg/kg body weight), administered 68 days apart. Throughout the study, all control queens displayed luteal activity and fluctuating fecal estradiol concentrations, whereas the LNG-treated queens displayed lower estradiol concentrations and no luteal activity after treatment. We conclude that LNG, when delivered as a cesium-irradiated, slow-release, injectable matrix, is an effective contraceptive in domestic cats, reducing follicular activity, and thus, preventing mating and luteal activity. Zoo Biol 20: [407][408][409][410][411][412][413][414][415][416][417][418][419][420][421] 2001.