Objective This paper was aimed to investigate the time-dependence of toxicity and pharmacodynamic action in Cyclophosphamide-Cisplatin-Adriamycin(CAP)combined chemotherapy and to find theoptimal administrating time to provide the better dosage regimen for the clinical cancer treatment.Methods S180 tumor bearing mice were firstly divided into six groups,and then were injected(ip.)with CTX(20 mg·kg-1),DDP(1 mg·kg-1),ADM(1 mg·kg-1)at different time(10:00 h,14:00 h,18:00 h,22:00 h,02:00 h and 06:00 h),respectively.In all groups ADM(1 mg·kg-1)were administed every three days.Finally the various related data was collected to assess the time-dependence of toxicity and pharmacodynamic action in CAP combined chemotherapy.Results The tumors could be inhibited by CAP combined chemotherapy in all the tested groups at different time,the group administed at 02:00 h showed the best action.The results of tumor cell cycle analysis showed that DNA synthesis decreased after the chemotherapy,most significantly at 22:00 h.The levels of tumor cell apoptosis-related proteins p53 and Bcl-2 increased after combination chemotherapy,whereas the level of Bax declined.And p53 changed most remarkably from 18:00 to 22:00 h,and for Bcl-2 and Bax that was from 02:00 to 10:00 h.The distribution of bone marrow cells cycle appeared sub-G1 peak,which is the phenomenon of apoptosis,at 02:00 h and 10:00 h was the most significant.At the same time the proportion of G1 and S-phase decreced,which indicates DNA synthesis of bone marrow cell declined.A time-dependent 19 KD activated fragments of Caspase-3 appeared by western blotting determination,at 02:00 h and 10:00 h.Conclusions The CAP combined chemotherapy had the best pharmacodynamic action during 22:00-02:00 h and the worst during the 10:00-14:00 h.As refer to toxicity,the most toxic time was during 06:00-14:00 h. Objective This paper was aimed to investigate the time-dependence of toxicity and pharmacodynamic action in Cyclophosphamide-Cisplatin-Adriamycin (CAP) combined chemotherapy and to find the optimized dosage to provide the better dosage regimen for the clinical cancer treatment. Methods S180 tumor bearing mice were treated with CTX (20 mg · kg -1), DDP (1 mg · kg -1) and ADM (1 mg · kg -1) at different times (10) : 00 h, 14:00 h, 18:00 h, 22:00 h, 02:00 h and 06:00 h), respectively.In all groups ADM (1 mg · kg-1) were administed every three days. Finally the various related data was collected to assess the time-dependence of toxicity and pharmacodynamic action in CAP combined chemotherapy. Results of the tumors could be inhibited by CAP combined chemotherapy in all the tested groups at different time, the group administed at 02:00 h showed the best action. The results of tumor cell cycle analysis showed that DNA synthesis decreased after the chemotherapy, most sign ificantly at 22:00 h. These levels of tumor cell apoptosis-related proteins p53 and Bcl-2 increased after combination chemotherapy, while the level of Bax declined. And p53 has been remarkably remarkably from 18:00 to 22:00 h, and for Bcl-2 and Bax that was from 02:00 to 10:00 h. The distribution of bone marrow cells cycle was sub-G1 peak, which is the phenomenon of apoptosis, at 02:00 h and 10:00 h was the most significant.At the same time the proportion of G1 and S-phase decreced, which indicates DNA synthesis of bone marrow cell declined. A time-dependent 19 KD activated fragments of Caspase-3 by western blotting determination, at 02:00 h and 10:00 h.Conclusions The CAP combined chemotherapy had the best pharmacodynamic action during 22: 00-02: 00 h and the worst during the 10: 00-14: 00 h. As to to toxicity, the most toxic time was during 06 : 00-14: 00 h.