Objective: To evaluate the effects of selective P receptor (PR) modulator CDB4124 on cell proliferation and apoptosis in cultured human uterine leiomyoma smooth muscle (LSM) cells and control myometrial smooth muscle (MSM) cells in matched uteri. Design: Laboratory research. Setting: Academic medical center. Patient(s): Premenopausal women (n = 12) undergoing hysterectomy for leiomyoma-related symptoms. Intervention(s): Treatment of primary LSM and MSM cells with CDB4124 (10-8-10-6 M) or vehicle for 24, 48, or 72 hours. Main Outcome Measure(s): Western blot for protein expression of proliferating cell nuclear antigen, cleaved polyadenosine 5′-diphosphate-ribose polymerase, Bcl-2, and Krüppel-like transcription factor 11; 93-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate viable cell numbers; and real-time polymerase chain reaction (PCR) to quantify messenger RNA (mRNA) levels. Result(s): Treatment with CDB4124 significantly decreased levels of the proliferation marker proliferating cell nuclear antigen, the number of viable LSM cells, and the antiapoptotic protein Bcl-2. On the other hand, treatment with CDB4124 increased levels of the apoptosis marker cleaved polyadenosine 5′-diphosphate-ribose polymerase and the tumor suppressor Krüppel-like transcription factor 11 in a dose- and time-dependent manner in LSM cells. In matched MSM cells, however, CDB4124 did not affect cell proliferation or apoptosis. Conclusion(s): CDB4124 selectively inhibits proliferation and induces apoptosis in LSM but not in MSM cells. © 2010 American Society for Reproductive Medicine.